The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index; none of the 11 sources its claims cite is checked for support yet.
B cells and tertiary lymphoid structures promote immunotherapy response
Open accessAbstract
Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers 1-10 and strategies to augment clinical response have largely focused on the T cell compartment. However, other immune subsets may also contribute to anti-tumour immunity 11-15, although these have been less well-studied in ICB treatment 16. A previously conducted neoadjuvant ICB trial in patients with melanoma showed via targeted expression profiling 17 that B cell signatures were enriched in the tumours of patients who respond to treatment versus non-responding patients. To build on this, here we performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumours of responders versus non-responders. Our findings were corroborated using a computational method (MCP-counter 18) to estimate the immune and stromal composition in this and two other ICB-treated cohorts (patients with melanoma and renal cell carcinoma). Histological evaluation highlighted the localization of B cells within tertiary lymphoid structures. We assessed the potential functional contributions of B cells via bulk and single-cell RNA sequencing, which demonstrate clonal expansion and unique functional states of B cells in responders. Mass cytometry showed that switched memory B cells were enriched in the tumours of responders. Together, these data provide insights into the potential role of B cells and tertiary lymphoid structures in the response to ICB treatment, with implications for the development of biomarkers and therapeutic targets.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
48 Own result · 19 Own method · 11 Own interpretation · 9 Not checked yet
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, these findings were corroborated in translational studies of separate cohorts of patients with melanoma36 and sarcoma37 who were treated with ICB.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells found in the tumours of responders
What the sources say
- Not checked yetcites [36] Cabrita, R. L. et al. Tertiary lymphoid structures improve immunotherapy and survival in melanoma. Nature https://doi.org/10.1038/s41586-019-1914-8 (2020). source
- Not checked yetcites [37] Petitprez, F. et al. B cells are associated with survival and immunotherapy response in sarcoma. Nature https://doi.org/10.1038/s41586-019-1906-8 (2020). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“B cells were not significantly associated with pathological response rates in an analogous trial of neoadjuvant-targeted therapy in patients with BRAF-mutated melanoma38”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells found in the tumours of responders
What the sources say
- Not checked yetcites [38] Amaria, R. N. et al. Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: a single-centre, open-label, randomised, phase 2 trial. Lancet Oncol. 19, 181–193 (2018). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Findings of high B cell lineage scores in responders were replicated in samples from an additional cohort of patients with melanoma treated with neoadjuvant versus adjuvant checkpoint blockade (ClinicalTrials.gov identifier NCT02437279, OpACIN-neo trial) (n = 12 responders, 6 non-responders)35”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells found in the tumours of responders
What the sources say
- Not checked yetcites [35] Blank, C. U. et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat. Med. 24, 1655–1661 (2018). source
plaincorrelationaln = 12- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“B cell signatures alone were predictive of response in univariable analyses (odds ratio 2.6, P = 0.02 for our trial, and odds ratio 2.9, P = 0.03 for combined melanoma cohorts)”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells found in the tumours of responders
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“but not in multivariable analyses when considering other components of the immune cell infiltrate”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells found in the tumours of responders
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In these analyses, we again observed enrichment of a B cell signature in responders versus non-responders at baseline and early on-treatment (P = 0.036 and 0.038, respectively).”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells found in the tumours of responders
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Gene expression profiling by microarray and subsequent MCP-counter analysis of baseline tumour samples was performed, demonstrating significantly higher expression of B-cell-related genes in responders versus non-responders (P = 0.0011, n = 17 responders and 11 non-responders)”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Similar B cell signature observed in RCC
boostedcorrelationaln = 17- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Other genes that are expected to alter the function of B cells were also significantly enriched in responders versus non-responders, such as FCRL5, IDO1, IFNG and BTLA.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells found in the tumours of responders
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“here we performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumours of responders versus non-responders.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“TLSs are associated with markers of T cell activation and response and B cell proliferation.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 23
- Probably not a substantial claim. 28
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“significantly higher expression of B-cell-related genes such as MZB1, JCHAIN and IGLL5 was observed in patients that respond to ICB treatment versus non-responding patients (‘responders’ and ‘non-responders’, hereafter) at baseline (P < 0.001) with over-representation of these genes compared to T cells and other immune markers (with evaluable tumours from seven responders and nine non-responders)”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells found in the tumours of responders
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Importantly, there was no clear association of MICs with known genomic subtypes of melanoma (BRAF, NRAS, NF1 or triple wild type)42 or disease site (nodal or non-nodal)”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells prognostic in TCGA analysis
What the sources say
- Not checked yetcites [42] Cancer Genome Atlas Network. Genomic classification of cutaneous melanoma. Cell 161, 1681–1696 (2015). source
plainn = 136- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pathway analysis was also performed on bulk RNA-seq data from our clinical trial cohort, revealing increased immune signalling pathways in responders than in non-responders, including T cell receptor signalling, major histocompatibility complex-mediated antigen presentation and processing, differentiation of T helper 1 and 2 (TH1 and TH2) cells, and costimulatory signalling associated with T cell”
§ B cells and tertiary lymphoid structures promote immunotherapy response > BCR and single-cell RNA-seq offer functional insight
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For tumour, this included 9 responders and 9 non-responders, and for peripheral blood mononuclear cells, 8 responders and 8 non-responders.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > Sample preparation and acquisition
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Similar analyses were performed to assess the expression of immune-related genes in clear-cell RCC from the TCGA (TCGA-KIRC, n = 526)43. In these analyses, similar immune classes were observed; however, immune infiltration was not associated with survival in these patients (P = 0.24)”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells prognostic in TCGA analysis
What the sources say
- Not checked yetcites [43] Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499, 43–49 (2013). source
plainn = 526- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“yielding a final stage III TCGA-SKCM cohort of n = 136.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > TCGA SKCM and KIRC data downloading and patient selection
plainn = 136- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“resulting in a median of approximately 1.4 million paired-end reads and a median of 2,588 genes detected per cell.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > Single-cell sequencing and analysis of CD45+ B cells
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The density of CD20+ B cells and TLSs, and the ratio of TLSs to tumour area were higher in responders than in non-responders in our neoadjuvant melanoma cohort, particularly in early on-treatment samples (P = 0.0008, P = 0.001 and P = 0.002, respectively), although statistical significance was not reached for all the markers in the baseline samples (P = 0.132, P = 0.078 and P = 0.037, respectively”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells localized in the context of TLSs
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we identified significantly increased clonal counts for both immunoglobulin heavy and light chains (IgH and IgL; P = 0.001 and P = 0.004, respectively) and increased BCR diversity in responders than in non-responders (P = 0.002 and P = 0.0008)”
§ B cells and tertiary lymphoid structures promote immunotherapy response > BCR and single-cell RNA-seq offer functional insight
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Other notable differences included an increase in plasma cells in responders compared with non-responders; however, this did not reach significance and was largely driven by data from one patient (P = 0.3)”
§ B cells and tertiary lymphoid structures promote immunotherapy response > CyTOF shows differential B cell phenotypes
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For TCGA-KIRC, the cases without available expression data were excluded and a total of 526 cases were taken into subsequent analysis.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > TCGA SKCM and KIRC data downloading and patient selection
plainn = 526- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No significant differences were identified when testing for associations of each individual cluster (G1–G4) with the clinical outcome, probably owing to limited sample size.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > BCR and single-cell RNA-seq offer functional insight
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Analogous immunohistochemical findings were observed in our cohort of patients with RCC treated with pre-surgical ICB, with increased infiltration of CD20+ cells and TLSs density associated with response to treatment (Extended Data Fig. 6b–d); these TLSs are morphologically similar to those found in melanoma”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells localized in the context of TLSs
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“TLSs are associated with response in RCC similar to those observed in melanoma.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Extended Data
plaincorrelationaln = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“tumours from responders had a significantly higher frequency of memory B cells, whereas non-responders had a significantly higher frequency of naive B cells (P = 0.033 for naive and P = 0.033 for memory)”
§ B cells and tertiary lymphoid structures promote immunotherapy response > CyTOF shows differential B cell phenotypes
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As in the case of melanoma, B cell signatures were predictive of a response in univariable analysis in the RCC cohort (odds ratio 61.2, P = 0.05) but not multivariable analysis”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Similar B cell signature observed in RCC
plaincorrelationaln = 17- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Survival data were missing for 9 of 136 samples, so n = 127 samples were available for overall survival analyses.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > TCGA SKCM and KIRC data downloading and patient selection
plainn = 127- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“we found that B cells were significantly enriched in tumours from responders versus non-responders and were predictive of a response (odds ratio 1.05, P = 0.02)”
§ B cells and tertiary lymphoid structures promote immunotherapy response > BCR and single-cell RNA-seq offer functional insight
What the sources say
- Not checked yetcites [44] Sade-Feldman, M. et al. Defining T cell states associated with response to checkpoint immunotherapy in melanoma. Cell 175, 998–1013 (2018). source
plaincorrelationaln = 48- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This process yielded a median robustness measure of 0.96 for the selected k=11.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > Unsupervised clustering of immune cells
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are 28 available pre-treatment samples from 3 arms: nivolumab (n = 6), nivolumab plus bevacizumab (n = 14) and nivolumab plus ipilimumab (n = 8).”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > Affymetrix microarray for RCC
plainn = 28- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“architectural analysis showed that CD20+ B cells were localized in TLSs of tumours of responders, and were colocalized with CD4+, CD8+and FOXP3+ T cells.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells localized in the context of TLSs
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which suggests that B cells probably act together with other immune subsets and are not acting in isolation”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells found in the tumours of responders
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“however, B cells have previously been shown to be positively associated with responses to chemotherapy in other cancer types39,40.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells found in the tumours of responders
What the sources say
- Not checked yetcites [39] Reddy, S. M. et al. Poor response to neoadjuvant chemotherapy correlates with mast cell infiltration in inflammatory breast cancer. Cancer Immunol. Res. 7, 1025–1035 (2019). source
- Not checked yetcites [40] Song, I. H. et al. Predictive value of tertiary lymphoid structures assessed by high endothelial venule counts in the neoadjuvant setting of triple-negative breast cancer. Cancer Res. Treat. 49, 399–407 (2017). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“however, sample size was again limited”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Similar B cell signature observed in RCC
plainn = 17- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“No statistical methods were used to predetermine sample size.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > Statistical analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The correlation matrix was carefully reviewed and the sequencing event generated from one library pool that showed poor correlation with other library pools from the same RNA sample were removed before sample-level merging of BAM files.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > RNA-seq data processing and quality check
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Samples with fewer than 200 CD45+CD19+ B cells were not used for downstream analyses.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > Data analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The observation of switched memory B cells (that can differentiate into plasma cells) in responders suggests that they could be potentially contributing to the anti-tumour response by producing antibodies against the tumours.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Summary
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Switched memory B cells can differentiate into plasma cells.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Representative transmission electron micrographs showing Dynabead with exosomes present after immunocapture.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Extended Data
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“for each patient, we collected and sequenced the same number of cells (n = 384 CD45+ cells per plate). Thus, the number of cells per patient is equal”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > Single-cell sequencing and analysis of CD45+ B cells
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“RNA quality was assessed on an Agilent 2100 Bioanalyzer using the Agilent RNA 6000 Nano Chip with smear analysis to determine DV200 and original RNA concentration.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > Gene expression profiling and analysis: RNA extraction for neoadjuvant melanoma ICB-treated cohort
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Technical replicates were constrained to n = 1 per time point, owing to limited tissue availability in patient-derived samples as well as prioritization for multiple studies.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > Statistical analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Nanoimager-captured images of the beads coated with CD63+ exosomes as compared with isotype control.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Extended Data
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Protein targets with a signal to noise ratio less than 2 were removed from downstream analysis.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > nCounter hybridization assay for photocleaved oligo counting
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Five random areas on each sample were analysed blindly by a pathologist at 20× magnification.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > Multiplex immunofluorescence assay and analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Only in-frame productive clonotypes were taken into subsequent analysis.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > B cell clonotype analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“These data represent combined tumour and peripheral blood samples from patients with melanoma treated with ICB ran together (8 tumour n = 5 R and n = 3 NR and 8 peripheral blood samples n = 4 R and n = 4 NR), thus eliminating batch effect.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Extended Data
plaindirectn = 8- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The experiments were not randomized”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > Statistical analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For one sample, the Nanosight measurement was erroneous and excluded. All samples were included in the flow cytometric analyses.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > Flow cytometric analyses of exosomes
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The reads that had ≥ 15 contiguous low-quality bases (phred score < 20) were removed from the FASTQ files.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > RNA-seq data processing and quality check
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“investigators were not blinded to allocation during experiments and outcome assessment unless stated otherwise.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > Statistical analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We identify similar mature TLSs in patients with extra-nodal metastases (Extended Data Fig. 5b), which suggests that TLSs may develop in non-nodal sites and are associated with the response to ICB treatment.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > B cells localized in the context of TLSs
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Responder versus non-responder status was blinded until flow cytometry data capture and FlowJo analyses were completed.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Methods > Flow cytometric analyses of exosomes
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
B cells can secrete cytokines including TNF, IL-2, IL-6, and IFNγ, and through these cytokines activate and recruit other immune effector cells including T cells.
“B cells can also secrete an array of cytokines (including TNF, IL-2, IL-6 and IFNγ), through which they activate and recruit other immune effector cells, including T cells.”
The paper relies on this without support.
Switched memory B cells can differentiate into plasma cells.
“switched memory B cells (that can differentiate into plasma cells)”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Also, as a member of the 12-chemokine gene signature classifier33, its expression has been correlated with the presence of tumor-associated tertiary lymphoid structures50–52 which are rapidly emerging as a powerful prognostic marker in melanoma and a number of other cancer types53–55.”
From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [54]
Experimental — accuracy not yet measuredIn the citing paper
“Tertiary lymphoid structures (TLS) have recently emerged as biomarkers of response to ICT across several tumor types, including lung cancer, melanoma, RCC, sarcoma, and urothelial cancer (163-167).”
From The Next Decade of Immune Checkpoint Therapy (2021) · cites this paper as [164]
In the citing paper
“Presence of B cells in tumor was associated with a better response to neoadjuvant therapy with ICB in melanoma and renal cell carcinoma (Cabrita et al., 2020; Helmink et al., 2020).”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Helmink et al., 2020
In the citing paper
“Tumor-infiltrating B cell populations in responder tumors were enriched in memory B cells; in contrast, naïve B cells were more prominent in non-responder tumors (Helmink et al., 2020).”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Helmink et al., 2020
In the citing paper
“Mounting evidence on the role of the gut and tumor microbiome, stress, and diet in tumor immunity and response to ICB (Helmink et al., 2020) has created a foundation for emerging adjunct therapies.”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Helmink et al., 2020
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ B cells and tertiary lymphoid structures promote immunotherapy response > Extended Data
“Figure: Extended Data Fig. 4 | Immune infiltrate is prognostic of improved diseasespecific survival in TCGA cutaneous melanoma cohort but not the clear-cell RCC cohort.”
§ B cells and tertiary lymphoid structures promote immunotherapy response > Extended Data
“b, Kaplan–Meier estimates of overall survival of MIC groups. c, Kaplan–Meier estimates of overall survival by B cell lineage scores shown by high and low groups dichotomized by median values.”
Citations
Cites
Cytoscape: A software Environment for integrated models of biomolecular interaction networks
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003) · Genome Research · doi:10.1101/gr.1239303 · Cited by 51,888 · cited 1×
“In the bulk-tissue, the differentially expressed genes which had a q-value <0.05 and log2foldchange >1.5 were & -1.5 were selected as input for network based pathway enrichment analysis using ReactomeFiViz 47 application in Cytoscape 48,49 .”
InfluentialSTAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · cited 1×
“5.3) 40 was then performed on the filtered FASTQ files with default parameters to generate RNA-seq BAM file for each sequencing event.”
Influentiallimma powers differential expression analyses for RNA-sequencing and microarray studies
Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv007 · Cited by 40,458 · cited 1×
“The Limma R software package 44 was used to identify DEGs from normalized microarray data for the RCC cohort.”
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464
Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors
Routy, B., Le Chatelier, E., Derosa, L., Duong, C. P. M., Alou, M. T., Daillère, R., Fluckiger, A., Messaoudene, M., Rauber, C., Roberti, M. P., et al. (2018) · Science · doi:10.1126/science.aan3706 · Cited by 5,671 · cited 2×
“Significant progress has been made in this regard, with the identification of several validated biomarkers, particularly for immune checkpoint blockade (ICB) 1-10 .”
Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients
Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., Prieto, P. A., Vicente, D., Hoffman, K., Wei, S. C., et al. (2018) · Science · doi:10.1126/science.aan4236 · Cited by 4,812
Self-citationCytoscape 2.8: new features for data integration and network visualization
Smoot, M. E., Ono, K., Ruscheinski, J., Wang, P., & Ideker, T. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq675 · Cited by 4,770
Controlling the false discovery rate in behavior genetics research
Benjamini, Y., Drai, D., Elmer, G., Kafkafi, N., & Golani, I. (2001) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00297-2 · Cited by 4,146
IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade
Ayers, M., Lunceford, J., Nebozhyn, M., Murphy, E., Loboda, A., Kaufman, D. R., Albright, A., Cheng, J. D., Kang, S. P., Shankaran, V., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci91190 · Cited by 3,788
Cited by
Sorted by citations
Zhang, Y., & Zhang, Z. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-0488-6 · Cited by 2,906
Tertiary lymphoid structures improve immunotherapy and survival in melanoma
Cabrita, R., Lauss, M., Sanna, A., Donia, M., Skaarup Larsen, M., Mitra, S., Johansson, I., Phung, B., Harbst, K., Vallon-Christersson, J., et al. (2020) · Nature · doi:10.1038/s41586-019-1914-8 · Cited by 2,374
Self-citationB cells are associated with survival and immunotherapy response in sarcoma
Petitprez, F., de Reyniès, A., Keung, E. Z., Chen, T. W.-W., Sun, C.-M., Calderaro, J., Jeng, Y.-M., Hsiao, L.-P., Lacroix, L., Bougoüin, A., et al. (2020) · Nature · doi:10.1038/s41586-019-1906-8 · Cited by 1,942
Self-citationHallmarks of response, resistance, and toxicity to immune checkpoint blockade
Morad, G., Helmink, B. A., Sharma, P., & Wargo, J. A. (2021) · Cell · doi:10.1016/j.cell.2021.09.020 · Cited by 1,648
Self-citationThe immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy
Bruni, D., Angell, H. K., & Galon, J. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0285-7 · Cited by 1,586
Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers
Hoshino, A., Kim, H. S., Bojmar, L., Gyan, K. E., Cioffi, M., Hernandez, J. M., Zambirinis, C. P., Rodrigues, G., Molina, H., Heissel, S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.009 · Cited by 1,275
“This finding is in accordance with studies demonstrating that tumor-infiltrating and systemic B cell responses are both predictive and indicative of responses to immunotherapy (Helmink et al., 2020).”
ResultTertiary lymphoid structures in cancer
Schumacher, T. N., & Thommen, D. S. (2022) · Science · doi:10.1126/science.abf9419 · Cited by 1,170
“Although a number of observations are consistentwith a model in which ICB affects TLS functionality (15, 136, 137), the evidence is still circumstantial.”
BackgroundResultInfluentialSelf-citationSchürch, C. M., Bhate, S. S., Barlow, G. L., Phillips, D. J., Noti, L., Zlobec, I., Chu, P., Black, S., Demeter, J., McIlwain, D. R., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.005 · Cited by 1,084
CD8+ T cell differentiation and dysfunction in cancer
Philip, M., & Schietinger, A. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-021-00574-3 · Cited by 1,052
Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics
Longo, S. K., Guo, M. G., Ji, A. L., & Khavari, P. A. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-021-00370-8 · Cited by 1,059
Sun, L., Su, Y., Jiao, A., Wang, X., & Zhang, B. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01471-y · Cited by 1,153
The cancer-immunity cycle: Indication, genotype, and immunotype
Mellman, I., Chen, D. S., Powles, T. B., & Turley, S. J. (2023) · Immunity · doi:10.1016/j.immuni.2023.09.011 · Cited by 1,018
Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition
Litchfield, K., Reading, J. L., Puttick, C., Thakkar, K., Abbosh, C., Bentham, R., Watkins, T. B. K., Rosenthal, R., Biswas, D., Rowan, A., et al. (2021) · Cell · doi:10.1016/j.cell.2021.01.002 · Cited by 893
“The selective expression of CCR5 and CXCL13 in neoantigen-specific T cells further suggests that a key feature of CPI-responsiveness is the ability to sustain ongoing priming and recruitment of tumour reactive T cells supported by CXCR5+ lymphocytes, which may include T and B cells (Helmink et al., 2020).”
Spatially organized multicellular immune hubs in human colorectal cancer
Pelka, K., Hofree, M., Chen, J. H., Sarkizova, S., Pirl, J. D., Jorgji, V., Bejnood, A., Dionne, D. A., Ge, W. H., Xu, K. H., et al. (2021) · Cell · doi:10.1016/j.cell.2021.08.003 · Cited by 917
“, 2016), contain germinal center B cells, and have been associated with high T cell activity, favorable prognosis, and effective response to immunotherapy (Cabrita et al., 2020; Coppola et al., 2011; Helmink et al., 2020; Petitprez et al., 2020; Sautès-Fridman et al., 2019).”
BackgroundSelf-citationTumor-infiltrating lymphocytes in the immunotherapy era
Paijens, S. T., Vledder, A., de Bruyn, M., & Nijman, H. W. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-00565-9 · Cited by 914
“Increased BCR diversity and clonal expansion were also observed in tumors of melanoma patients.(75) Of note, some autoantibodies have also been found to be tumor promoting.”
BackgroundMeylan, M., Petitprez, F., Becht, E., Bougoüin, A., Pupier, G., Calvez, A., Giglioli, I., Verkarre, V., Lacroix, G., Verneau, J., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.02.001 · Cited by 831
Self-citationProvencio, M., Nadal, E., Insa, A., García-Campelo, M. R., Casal-Rubio, J., Dómine, M., Majem, M., Rodríguez-Abreu, D., Martínez-Martí, A., De Castro Carpeño, J., et al. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(20)30453-8 · Cited by 841
A single-cell map of intratumoral changes during anti-PD1 treatment of patients with breast cancer
Bassez, A., Vos, H., Van Dyck, L., Floris, G., Arijs, I., Desmedt, C., Boeckx, B., Vanden Bempt, M., Nevelsteen, I., Lambein, K., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01323-8 · Cited by 867
The Next Decade of Immune Checkpoint Therapy
Sharma, P., Siddiqui, B. A., Anandhan, S., Yadav, S. S., Subudhi, S. K., Gao, J., Goswami, S., & Allison, J. P. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1680 · Cited by 750
Self-citationZhang, Y., Chen, H., Mo, H., Hu, X., Gao, R., Zhao, Y., Liu, B., Niu, L., Sun, X., Yu, X., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.09.010 · Cited by 783
Ott, P. A., Hu-Lieskovan, S., Chmielowski, B., Govindan, R., Naing, A., Bhardwaj, N., Margolin, K., Awad, M. M., Hellmann, M. D., Lin, J. J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.053 · Cited by 738
The Lymphatic Vasculature in the 21st Century: Novel Functional Roles in Homeostasis and Disease
Oliver, G. C., Kipnis, J., Randolph, G. J., & Harvey, N. L. (2020) · Cell · doi:10.1016/j.cell.2020.06.039 · Cited by 701
Fridman, W. H., Meylan, M., Petitprez, F., Sun, C., Italiano, A., & Sautès‐Fridman, C. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00619-z · Cited by 710
Self-citationVanhersecke, L., Brunet, M., Guégan, J., Rey, C., Bougoüin, A., Cousin, S., Moulec, S. L., Besse, B., Loriot, Y., Larroquette, M., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00232-6 · Cited by 647
Self-citationB cells, plasma cells and antibody repertoires in the tumour microenvironment
Sharonov, G. V., Serebrovskaya, E. O., Yuzhakova, D. V., Britanova, O. V., & Chudakov, D. M. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-019-0257-x · Cited by 630
The Tumor Microenvironment in the Response to Immune Checkpoint Blockade Therapies
Petitprez, F., Meylan, M., de Reyniès, A., Sautès‐Fridman, C., & Fridman, W. H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00784 · Cited by 621
Self-citationMicrobiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment
Lam, K. C., Araya, R. E., Huang, A., Chen, Q., Di Modica, M., Rodrigues, R. R., Lopès, A., Johnson, S. B., Schwarz, B., Bohrnsen, E., et al. (2021) · Cell · doi:10.1016/j.cell.2021.09.019 · Cited by 604
Self-citationHuang, A. C. C., & Zappasodi, R. (2022) · Nature Immunology · doi:10.1038/s41590-022-01141-1 · Cited by 586
de Almeida, L. G. N., Thode, H., Eslambolchi, Y., Chopra, S., Young, D. W., Gill, S. E., Devel, L., & Dufour, A. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.121.000349 · Cited by 572
Tumour-infiltrating B cells: immunological mechanisms, clinical impact and therapeutic opportunities
Laumont, C. M., Banville, A. C., Gilardi, M., Hollern, D. P., & Nelson, B. H. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00466-1 · Cited by 565
Spatial profiling technologies illuminate the tumor microenvironment
Elhanani, O., Ben-Uri, R., & Keren, L. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.01.010 · Cited by 546
Targeting the gut and tumor microbiota in cancer
Park, E. M., Chelvanambi, M., Bhutiani, N., Kroemer, G., Zitvogel, L., & Wargo, J. A. (2022) · Nature Medicine · doi:10.1038/s41591-022-01779-2 · Cited by 496
Self-citationIntratumoural administration and tumour tissue targeting of cancer immunotherapies
Melero, I., Álvarez, E. C., Álvarez, M., Champiat, S., & Marabelle, A. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00507-y · Cited by 505
Cui, C., Wang, J., Fagerberg, E., Chen, P.-M., Connolly, K. A., Damo, M., Cheung, J. F., Mao, T., Askari, A. S., Chen, S., et al. (2020) · Cell · doi:10.1016/j.cell.2021.11.007 · Cited by 493
Self-citationFu, T., Dai, L.-J., Wu, S.-Y., Xiao, Y., Ma, D., Jiang, Y.-Z., & Shao, Z.-M. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01103-4 · Cited by 480
“Tertiary lymphoid structures (TLSs) are ectopic hyperplasia lymphoid tissues located outside the immune organs (85) that are present in a fraction of specific types of tumors.”
MethodInfluentialAndersson, A., Larsson, L., Stenbeck, L., Salmén, F., Ehinger, A., Wu, S. Z., Al-Eryani, G., Roden, D., Swarbrick, A., Borg, Å., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26271-2 · Cited by 404
Magen, A., Hamon, P., Fiaschi, N., Soong, B. Y., Park, M. D., Mattiuz, R., Humblin, E., Troncoso, L., D’souza, D., Dawson, T., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02345-0 · Cited by 429
Intratumoral plasma cells predict outcomes to PD-L1 blockade in non-small cell lung cancer
Patil, N. S., Nabet, B. Y., Müller, S., Koeppen, H., Zou, W., Giltnane, J. M., Au‐Yeung, A., Srivats, S., Cheng, J. H., Takahashi, C., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.02.002 · Cited by 423
Enhancing anti-tumour efficacy with immunotherapy combinations
Meric‐Bernstam, F., Larkin, J., Tabernero, J. M., & Bonini, C. (2020) · The Lancet · doi:10.1016/s0140-6736(20)32598-8 · Cited by 432
van Dijk, N., Gil-Jimenez, A., Siliņa, K., Hendricksen, K., Smit, L. A., de Feijter, J. M., van Montfoort, M. L., van Rooijen, C. C. N., Peters, D. D. G. C., Broeks, A., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1085-z · Cited by 415
Self-citationGrasso, C. S., Tsoi, J., Onyshchenko, M., Abril-Rodriguez, G., Ross-Macdonald, P., Wind-Rotolo, M., Champhekar, A., Medina, E., Torrejon, D. Y., Shin, D. S., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.08.005 · Cited by 390
“, 2018), but they also need to analyze the composition of the immune infiltrate and its expression of immune activating gene programs (Auslander et al., 2018; Ayers et al., 2017; Cabrita et al., 2020; Chen et al., 2016; Cristescu et al., 2018; Fehrenbacher et al., 2016; Gide et al., 2019; Helmink et al., 2020; Jerby-A…”
BackgroundResultSTING Agonists as Cancer Therapeutics
Amouzegar, A., Chelvanambi, M., Filderman, J. N., Storkus, W. J., & Luke, J. J. (2021) · Cancers · doi:10.3390/cancers13112695 · Cited by 419
ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis
Griss, J., Viteri, G., Sidiropoulos, K., Nguyen, V., Fabregat, A., & Hermjakob, H. (2020) · Molecular & Cellular Proteomics · doi:10.1074/mcp.tir120.002155 · Cited by 418
Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy
Cai, L., Li, Y., Tan, J., Xu, L., & Li, Y. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01499-1 · Cited by 423
“Mechanistically, the chemokine CXCL13 in the TME may play a crucial role as a B cell attractant [192].”
BackgroundAn ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer
Voabil, P., de Bruijn, M., Roelofsen, L. M., Hendriks, S. H., Brokamp, S., van den Braber, M., Broeks, A., Sanders, J., Herzig, P., Zippelius, A., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01398-3 · Cited by 380
Self-citationHu, J., Zhang, L., Xia, H., Yan, Y., Zhu, X., Sun, F., Sun, L., Li, S., Li, D., Wang, J., et al. (2023) · Genome Medicine · doi:10.1186/s13073-023-01164-9 · Cited by 410
“Other studies have indicated that the formation of tertiary lymphoid structures (TLS), which are aggregations of B cells, T cells, dendritic cells (DC), and high endothelial venules, promote immunotherapy response [13].”
BackgroundResultInsights Gained from Single-Cell Analysis of Immune Cells in the Tumor Microenvironment
Ren, X., Zhang, L., Zhang, Y., Li, Z., Siemers, N. O., & Zhang, Z. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-110519-071134 · Cited by 374
Towards targeting the breast cancer immune microenvironment
Harris, M. A., Savas, P. S., Virassamy, B., O’Malley, M. M. R., Kay, J., Mueller, S. N., Mackay, L. K., Salgado, R., & Loi, S. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00714-6 · Cited by 409
“…TLSs in breast cancer TME are not yet clear, neither are there internationally accepted criteria on how to define or quantify TLSs using histopathological slides; however, studies in renal cell carcinoma and melanoma have found both TLSs and B cells are associated with good responses to ICB 60 .”
Ho, W. J., Zhu, Q., Durham, J., Popovic, A., Xavier, S., Leatherman, J., Mohan, A., Mo, G., Zhang, S., Gross, N., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00234-4 · Cited by 360
Self-citationDissecting Esophageal Squamous-Cell Carcinoma Ecosystem by Single-Cell Transcriptomic Analysis
Zhang, X., Peng, L., Luo, Y., Zhang, S., Pu, Y., Chen, Y., Guo, W., Yao, J., Shao, M., Fan, W., et al. (2020) · Nature Communications · doi:10.1038/s41467-021-25539-x · Cited by 385
Self-citationRuffin, A. T., Cillo, A. R., Tabib, T., Liu, A., Onkar, S., Kunning, S. R., Lampenfeld, C., Atiya, H. I., Abécassis, I., Kürten, C. H. L., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23355-x · Cited by 377
Yang, L., Chu, Z., Liu, M., Zou, Q., Li, J., Liu, Q., Wang, Y., Wang, T., Xiang, J., & Wang, B. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01453-1 · Cited by 383
“Because B cells are critical for tertiary lymphoid structures (TLS), a tumor infiltrated ectopic lymphoid organ similar to SLOs, multiple studies found the higher number of infiltrating B cells in TLS indicate a better patient survival with malignant tumors, however the mechanism remains unclear [168, 169].”
Role of B cells as antigen presenting cells
Rastogi, I., Jeon, D., Moseman, J. E., Muralidhar, A., Potluri, H. K., & McNeel, D. G. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.954936 · Cited by 352
“Several groups have also shown that the presence of TLS is associated with response to immune checkpoint blockade (11, 13, 14).”
BackgroundMoving towards personalized treatments of immune-related adverse events
Esfahani, K., Elkrief, A., Calabrese, C., Lapointe, R., Hudson, M., Routy, B., Miller, W. H., & Calabrese, L. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0352-8 · Cited by 351
STING-induced regulatory B cells compromise NK function in cancer immunity
Li, S., Mirlekar, B., Johnson, B. M., Brickey, W. J., Wrobel, J. A., Yang, N., Song, D., Entwistle, S., Tan, X. M., Deng, M., et al. (2022) · Nature · doi:10.1038/s41586-022-05254-3 · Cited by 359
Neoadjuvant relatlimab and nivolumab in resectable melanoma
Amaria, R. N., Postow, M. A., Burton, E. M., Tetzlaff, M. T., Ross, M. I., Torres-Cabala, C. A., Glitza, I. C., Duan, F., Milton, D. R., BUSAM, K. J., et al. (2022) · Nature · doi:10.1038/s41586-022-05368-8 · Cited by 356
Self-citationTreatment of Advanced Melanoma in 2020 and Beyond
Jenkins, R. W., & Fisher, D. E. (2020) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.03.943 · Cited by 365
Principles and therapeutic applications of adaptive immunity
Chi, H., Pepper, M., & Thomas, P. G. (2024) · Cell · doi:10.1016/j.cell.2024.03.037 · Cited by 394
Immunotherapy combination approaches: mechanisms, biomarkers and clinical observations
Butterfield, L. H., & Najjar, Y. G. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00973-8 · Cited by 372
Self-citationLymph node stromal cells: cartographers of the immune system
Krishnamurty, A. T., & Turley, S. J. (2020) · Nature Immunology · doi:10.1038/s41590-020-0635-3 · Cited by 338
Tertiary lymphoid structures and B cells: An intratumoral immunity cycle
Fridman, W. H., Meylan, M., Pupier, G., Calvez, A., Hernández-Verdín, I., & Sautès‐Fridman, C. (2023) · Immunity · doi:10.1016/j.immuni.2023.08.009 · Cited by 343
Self-citationThe roles of tertiary lymphoid structures in chronic diseases
Sato, Y., Siliņa, K., van den Broek, M. F., Hirahara, K., & Yanagita, M. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00706-z · Cited by 326
“A single-cell RNA sequencing analysis of B cells derived from human tumours identified unswitched IgD + B cells, switched IgG + B cells and a wide range of B cells that expressed genes that are associated with immature or mature germinal centres 11,12 .”
InfluentialGao, J., Navai, N., Alhalabi, O., Siefker-Radtke, A., Campbell, M. T., Tidwell, R. S., Guo, C. C., Kamat, A. M., Matin, S. F., Araujo, J. C., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1086-y · Cited by 318
Self-citationOveracre-Delgoffe, A. E., Bumgarner, H. J., Cillo, A. R., Burr, A. H. P., Tometich, J. T., Bhattacharjee, A., Bruno, T. C., Vignali, D. A. A., & Hand, T. W. (2021) · Immunity · doi:10.1016/j.immuni.2021.11.003 · Cited by 318
Monocytes in the Tumor Microenvironment
Ugel, S., Canè, S., Sanctis, F. D., & Bronte, V. (2021) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012418-013058 · Cited by 327
Cancer organoids 2.0: modelling the complexity of the tumour immune microenvironment
Polak, R., Zhang, E., & Kuo, C. J. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00706-6 · Cited by 347
“Studying patient-derived tissue sections of ICB responders and non-responders, single-cell RNA sequencing has been combined with mass cytometry to define the potential role of B cells and TLSs during ICB 14 .”
Improving head and neck cancer therapies by immunomodulation of the tumour microenvironment
Ruffin, A. T., Li, H., Vujanovic, L. N., Zandberg, D. P., Ferris, R. L., & Bruno, T. C. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00531-9 · Cited by 326
Rivellese, F., Surace, A. E. A., Goldmann, K., Sciacca, E., Çubuk, C., Giorli, G., John, C. R., Nerviani, A., Fossati‐Jimack, L., Thorborn, G., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01789-0 · Cited by 320
Self-citationDefining clinically useful biomarkers of immune checkpoint inhibitors in solid tumours
Holder, A. M., Dedeilia, A., Sierra-Davidson, K., Cohen, S., Liu, D., Parikh, A. R., & Boland, G. M. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00705-7 · Cited by 330
Tertiary lymphoid structures in anticancer immunity
Teillaud, J., Houel, A., Panouillot, M., Riffard, C., & Dieu‐Nosjean, M. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00728-0 · Cited by 322
“Moreover, this predictive status is specifically linked to B cells of TLS in several types of solid tumour 25,105,106,157 .”
InfluentialImmune-related toxicities of checkpoint inhibitors: mechanisms and mitigation strategies
Sullivan, R. J., & Weber, J. S. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00259-5 · Cited by 312
Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer
Lin, J., Wang, S., Coy, S., Chen, Y., Yapp, C., Tyler, M., Nariya, M. K., Heiser, C. N., Lau, K. S., Santagata, S., et al. (2023) · Cell · doi:10.1016/j.cell.2022.12.028 · Cited by 297
“50,51 Pathology inspection of 47 individual sections of CRC1 (22 H&E and 25 CyCIF) identified over 900 distinct SLO and TLS domains in2D (Figures 6A and S5A).”
BackgroundApplying high-dimensional single-cell technologies to the analysis of cancer immunotherapy
Gohil, S. H., Iorgulescu, J. B., Braun, D. A., Keskin, D. B., & Livak, K. J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-00449-x · Cited by 282
How chemokines organize the tumour microenvironment
Mempel, T. R., Lill, J. K., & Altenburger, L. M. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00635-w · Cited by 317
B Cell Function in the Tumor Microenvironment
Downs‐Canner, S., Meier, J. A., Vincent, B. G., & Serody, J. S. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101220-015603 · Cited by 306
Horvath, L., Thienpont, B., Zhao, L., Wolf, D. G. F., & Pircher, A. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01260-z · Cited by 288
“Especially those B cells located in mature TLS may exhibit immunostimulatory functions by closely interacting with local T cells, thereby enhancing anti-cancer immunity.”
BackgroundResultInfluentialRelevance of immune cell and tumor microenvironment imaging in the new era of immunotherapy
Galli, F., Aguilera, J. V., Palermo, B., Markovic, S. N., Nisticò, P., & Signore, A. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01586-y · Cited by 286
“From the clinical point of view, it is urgent to understand whether the presence and localization of TLS in pretreatment or longitudinal tumor tissue samples during and post-treatment, may be validated as prognostic/ predictive of responses to checkpoint blockade, with far reaching clinical implications, as recently r…”
BackgroundBreast tumor microenvironment structures are associated with genomic features and clinical outcome
Danenberg, E., Bardwell, H. A., Zanotelli, V. R., Provenzano, E., Chin, S., Rueda, O. M., Green, A. R., Rakha, E. A., Aparicio, S. A. J. R., Ellis, I. O., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01041-y · Cited by 273
“By contrast, TME cell diversity differed markedly: There was higher diversity among ER-negative subtypes (Basal; IntClusts 4, 5, and 10) and lesser diversity among indolent ER-positive subtypes (Luminal A; IntClusts 3 and 8).”
Rodriguez, A. B., Peske, J. D., Woods, A. N., Leick, K. M., Mauldin, I. S., Meneveau, M. O., Young, S. J., Lindsay, R. S., Melssen, M. M., Cyranowski, S., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109422 · Cited by 286
“Recent publications reported that TA-TLS presence prior to treatment was associated with a favorable response to immunotherapy in patients with cancer (Griss et al., 2019; Cabrita et al., 2020; Petitprez et al., 2020; Helmink et al., 2020).”
Zhang, Z., Wang, Z., Chen, Y., Wu, H., Yin, L., Zhao, Q., Luo, H., Zeng, Z.-L., Qiu, M., & Xu, R. (2022) · Genome Medicine · doi:10.1186/s13073-022-01050-w · Cited by 282
Drug-microbiota interactions: an emerging priority for precision medicine
Zhao, Q. C., Chen, Y., Huang, W., Zhou, H., & Zhang, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01619-w · Cited by 309
“277 Collectively, these studies indicate that the mouse and human gut microbiota may play a crucial role in regulating tumor IVDR on ICIs by modulating the host immune system.”
BackgroundWang, R., Dang, M., Harada, K., Han, G., Wang, F., Pizzi, M. P., Zhao, M., Tatlonghari, G., Zhang, S., Hao, D., et al. (2021) · Nature Medicine · doi:10.1038/s41591-020-1125-8 · Cited by 278
Self-citationDiao, J. A., Wang, J. K., Chui, W. F., Mountain, V., Gullapally, S. C., Srinivasan, R., Mitchell, R. N., Glass, B., Hoffman, S., Rao, S. K., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21896-9 · Cited by 289
Asrir, A., Tardiveau, C., Coudert, J., Laffont, R., Blanchard, L., Bellard, E., Veerman, K. M., Bettini, S., Lafouresse, F., Vina, E., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.01.002 · Cited by 286
CXCR4 inhibition in human pancreatic and colorectal cancers induces an integrated immune response
Biasci, D., Smoragiewicz, M., Connell, C. M., Wang, Z., Gao, Y., Thaventhiran, J. E. D., Basu, B., Magiera, Ł., Johnson, T. I., Bax, L., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2013644117 · Cited by 271
Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma
Au, L., Hatipoglu, E., de Massy, M. R., Litchfield, K., Beattie, G., Rowan, A., Schnidrig, D., Thompson, R. H., Byrne, F., Horswell, S. D., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.10.001 · Cited by 262
Self-citationPeña-Romero, A. C., & Orenes‐Piñero, E. (2022) · Cancers · doi:10.3390/cancers14071681 · Cited by 271
Hammerl, D., Martens, J. W. M., Timmermans, M., Smid, M., Trapman-Jansen, A. M., Foekens, R., Isaeva, O. I., Voorwerk, L., Balcioglu, H. E., Wijers, R., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25962-0 · Cited by 262
Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer
Liu, S., Zhang, X., Wang, W., Li, X., Sun, X., Zhao, Y., Wang, Q., Li, Y., Hu, F., & Ren, H. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02165-x · Cited by 300
Spatially aware dimension reduction for spatial transcriptomics
Shang, L., & Zhou, X. (2022) · Nature Communications · doi:10.1038/s41467-022-34879-1 · Cited by 256
“Importantly, we found that the detected immune cell region resembles a tertiary lymphoid structure (TLS) 60,61 with multiple features of TLS: the region is located near the tumor; the region primarily contains T cells and B cells, all of which are key cell types in TLS 60,62 – 64 ; the region is…”
BackgroundPre-metastatic niche: formation, characteristics and therapeutic implication
Wang, Y., Jia, J., Wang, F., Fang, Y., Yang, Y., Zhou, Q., Yuan, W., Gu, X., Hu, J., & Yang, S. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01937-7 · Cited by 289
“91,92 Conversely, under particular circumstances, such as regulatory B cells and regulatory T cells (Tregs), T and B cells can also act in an immunosuppressive capacity.”
BackgroundDing, G., Ma, J., Yun, J., Chen, X., Yu, L., Zhang, S., Shi, J.-Y., Chang, Y., Ji, Y., Wang, X., et al. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.10.030 · Cited by 256
Self-citationHoch, T., Schulz, D., Eling, N., Gómez, J. M. M., Levesque, M. P., & Bodenmiller, B. (2022) · Science Immunology · doi:10.1126/sciimmunol.abk1692 · Cited by 253
Laumont, C. M., & Nelson, B. H. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.017 · Cited by 269
Radiation-induced tumor immune microenvironments and potential targets for combination therapy
Guo, S., Yao, Y., Tang, Y., Xin, Z., Wu, D., Ni, C., Huang, J., Wei, Q., & Zhang, T. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01462-z · Cited by 290
IgA transcytosis and antigen recognition govern ovarian cancer immunity
Biswas, S., Mandal, G., Payne, K. K., Anadon, C. M., Gatenbee, C., Chaurio, R. A., Costich, T. L., Segura, C. M., Harro, C. M., Rigolizzo, K. E., et al. (2021) · Nature · doi:10.1038/s41586-020-03144-0 · Cited by 255
Li, Q., Liu, X., Wang, D., Wang, Y., Lu, H., Wen, S., Fang, J., Cheng, B., & Wang, Z. (2020) · International Journal of Oral Science · doi:10.1038/s41368-020-00092-3 · Cited by 254
Hot and cold tumors: Immunological features and the therapeutic strategies
Wang, L., Geng, H., Liu, Y., Liu, L., Chen, Y., Wu, F., Liu, Z., Ling, S., Wang, Y., & Zhou, L. (2023) · MedComm · doi:10.1002/mco2.343 · Cited by 261
Self-citationMechanisms of immune activation and regulation: lessons from melanoma
Kalaora, S., Nagler, A., Wargo, J. A., & Samuels, Y. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00442-9 · Cited by 252
“Understanding the different interactions that occur within the TLSs, as well as the mechanism of TLS formation, may suggest ways to induce TLS formation in non-immunogenic tumours.”
BackgroundInfluentialSelf-citationUnraveling B cell trajectories at single cell resolution
Morgan, D., & Tergaonkar, V. (2022) · Trends in Immunology · doi:10.1016/j.it.2022.01.003 · Cited by 239
Metadata
- Authors
- Helmink, B. A., Reddy, S. M., Gao, J., Zhang, S., Basar, R., Thakur, R., Yizhak, K., Sade-Feldman, M., Blando, J., Han, G., Gopalakrishnan, V., Xi, Y., Zhao, H., Amaria, R. N., Tawbi, H. A., Cogdill, A. P., Liu, W., LeBleu, V. S., Kugeratski, F. G., Patel, S., Davies, M. A., Hwu, P., Lee, J. E., Gershenwald, J. E., Lucci, A., Arora, R., Woodman, S., Keung, E. Z., Gaudreau, P.-O., Reuben, A., Spencer, C. N., Burton, E. M., Haydu, L. E., Lazar, A. J., Zapassodi, R., Hudgens, C. W., Ledesma, D. A., Ong, S., Bailey, M., Warren, S., Rao, D., Krijgsman, O., Rozeman, E. A., Peeper, D., Blank, C. U., Schumacher, T. N., Butterfield, L. H., Zelazowska, M. A., McBride, K. M., Kalluri, R., Allison, J., Petitprez, F., Fridman, W. H., Sautès-Fridman, C., Hacohen, N., Rezvani, K., Sharma, P., Tetzlaff, M. T., Wang, L., & Wargo, J. A.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Massachusetts General Hospital (US)
- Broad Institute (US)
- Parker Institute for Cancer Immunotherapy (US)
- Nanostring Technologies (United States) (US)
- The Netherlands Cancer Institute (NL)
- University of Pittsburgh (US)
- Inserm (FR)
- Corresponding author
- Helmink, Beth A.
- Wargo, Jennifer A.
- ORCID
- Helmink, Beth A.
- Reddy, Sangeetha M.
- Gao, Jianjun
- Zhang, Shaojun
- Thakur, Rohit
- Yizhak, Keren
- Sade-Feldman, Moshe
- Blando, Jorge
- Han, Guangchun
- Gopalakrishnan, Vancheswaran
- Xi, Yuanxin
- Zhao, Hao
- Liu, Wenbin
- LeBleu, Valerie S.
- Kugeratski, Fernanda G.
- Patel, Sapna
- Davies, Michael A.
- Hwu, Patrick
- Lee, Jeffrey E.
- Gershenwald, Jeffrey E.
- Lucci, Anthony
- Arora, Reetakshi
- Woodman, Scott
- Keung, Emily Z.
- Gaudreau, Pierre-Olivier
- Reuben, Alexandre
- Spencer, Christine N.
- Burton, Elizabeth M.
- Haydu, Lauren E.
- Lazar, Alexander J.
- Hudgens, Courtney W.
- Rao, Disha
- Krijgsman, Oscar
- Rozeman, Elisa A.
- Peeper, Daniel
- Blank, Christian U.
- Schumacher, Ton N.
- Zelazowska, Monika A.
- McBride, Kevin M.
- Kalluri, Raghu
- Allison, James
- Petitprez, Florent
- Fridman, Wolf Herman
- Hacohen, Nir
- Rezvani, Katayoun
- Sharma, Padmanee
- Wang, Linghua
- Wargo, Jennifer A.
- Venue
- Nature
- Published
- 2020-01-15
- Volume
- 577
- Issue
- 7791
- Pages
- 549-555
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC8762581
- OpenAlex
- W2998795792
- Cited by
- 2,731
- References
- 66
- Citations by year
- 2026: 422 · 2025: 422 · 2024: 458 · 2023: 393 · 2022: 433 · 2021: 383 · 2020: 217
- FWCI
- 129.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- AIM at Melanoma
- Parker Institute for Cancer Immunotherapy
- National Institutes of Health (W81XWH, CA- 016672)
- University of Texas MD Anderson Cancer Center ((CA016672), T32 CA 009599, P30-CA-016672)
- National Cancer Institute (T32CA009666, R01CA213233, CA213233, R01CA195733, CA195733, P30CA008748, T32CA009599, P30CA016672, P01CA117969)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- B cells, tertiary lymphoid structures, immune checkpoint blockade, cancer immunotherapy response, melanoma, renal cell carcinoma, switched memory B cells, B cell clonal expansion, tumor immune microenvironment, predictive biomarkers, MCP-counter, tumor-infiltrating immune cells
- MeSH terms
- Tertiary Lymphoid Structures, RNA-Seq, B-Lymphocytes, Carcinoma, Renal Cell, Clone Cells, Humans, Immunologic Memory, Immunotherapy, Melanoma, Neoplasm Metastasis, Phenotype, Prognosis, Receptors, Immunologic, Mass Spectrometry, T-Lymphocytes, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Dendritic Cells, Follicular, Single-Cell Analysis, Cell Cycle Checkpoints, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
