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.
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48 Own result · 19 Own method · 11 Own interpretation · 9 Not checked yet
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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- 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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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- 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.
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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.
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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.
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- 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
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InfluentialSTAR: ultrafast universal RNA-seq aligner
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Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients
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IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade
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Cited by
Sorted by citations
Items 501–600 of 1,004
Mapping Breast Cancer Microenvironment Through Single-Cell Omics
Tan, Z., Chen, K., Sun, M., Yang, F., Wong, M., Wang, S., & Zheng, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.868813 · Cited by 55
“Recently, B cells were associated to ICB response in renal cell carcinoma (37), melanoma (38), and sarcoma (39).”
BackgroundWei, J., Lu, X., Liu, Q., Fu, Y. S., Liu, S., Zhao, Y., Zhou, J., Chen, H., Wang, M., Li, L., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40480-x · Cited by 52
“After neoadjuvant treatment, enhanced CD20 + B cell in fi ltration was found in patients achieving pCR than in patients not achieving pCR.”
InfluentialImmunotherapy-related biomarkers: Confirmations and uncertainties
Catalano, M., Iannone, L. F., Nesi, G., Nobili, S., Mini, E., & Roviello, G. (2023) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2023.104135 · Cited by 61
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Zhang, L., Zhang, B., Zhang, M.-J., Li, W., Li, H., Jiao, Y., Yang, Q., Wang, S., Liu, Y., Song, A., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55430-4 · Cited by 55
“TLS arises in the context of in fl ammatory conditions and is characterized by the structured aggregation of leukocytes and consists of an inner B cell zone interspersed with T cells 7 .”
The emerging role of T follicular helper (TFH) cells in aging: Influence on the immune frailty
Varricchi, G., Bencivenga, L., Poto, R., Pecoraro, A., Shamji, M. H., & Rengo, G. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101071 · Cited by 54
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Tumor-Associated Neutrophils Drive B-cell Recruitment and Their Differentiation to Plasma Cells
Shaul, M. E., Zlotnik, A., Tidhar, E., Schwartz, A., Arpinati, L., Kaisar-Iluz, N., Mahroum, S., Mishalian, I., & Fridlender, Z. G. (2021) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-0839 · Cited by 49
“In a melanoma cohort, Helmink and colleagues (54) report higher density of CD20þ B cells and TLSs in responders compared with nonresponders to immune checkpoint blockade.”
BackgroundClubb, J. H. A., Kudling, T. V., Heiniö, C., Basnet, S., Pakola, S. A., Cervera-Carrascón, V., Santos, J. M., Quixabeira, D. C. A., Havunen, R., Sorsa, S., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.794251 · Cited by 51
“This is consistent with our understanding of IL-2 and ICI in circumventing T cell exhaustion and TLSs which are recognized as a place where T cell and B cell responses occur (28, 29).”
BackgroundResultscRNA-seq of colorectal cancer shows regional immune atlas with the function of CD20+ B cells
Ji, L., Fu, G., Huang, M., Kao, X., Zhu, J., Dai, Z., Chen, Y., Li, H., Zhou, J., Chu, X., et al. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216664 · Cited by 50
T cell exhaustion initiates tertiary lymphoid structures and turbocharges cancer-immunity cycle
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Poran, A., Scherer, J., Bushway, M. E., Besada, R. H., Balogh, K. N., Wanamaker, A., Williams, R. G., Prabhakara, J., Ott, P. A., Hu‐Lieskovan, S., et al. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100141 · Cited by 49
“A class-switched memory B cell phenotype also correlated with PC1, which might be related to recent findings of the involvement of these cells in the tumor microenvironment in patients responding to ICI.(31) The relative contribution of each of these features to PC1 demonstrated by the loadings (Figure 4B) points to t…”
BackgroundThe liver as an immunological barrier redefined by single‐cell analysis
Stamataki, Z., & Swadling, L. (2020) · Immunology · doi:10.1111/imm.13193 · Cited by 48
Fascin inhibitor increases intratumoral dendritic cell activation and anti-cancer immunity
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Single-cell sequencing reveals antitumor characteristics of intratumoral immune cells in old mice
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Progresses in biomarkers for cancer immunotherapy
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The role of CD4+ T cells in tumor and chronic viral immune responses
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Lymphoid organ-targeted nanomaterials for immunomodulation of cancer, inflammation, and beyond
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Highly Multiplexed Tissue Imaging in Precision Oncology and Translational Cancer Research
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“Other multicellular structures, such as tertiary lymphoid structures, stratify melanoma patients into responders and non-responders to immunotherapy (59, 60).”
BackgroundNeoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells
Goff, P. H., Riolobos, L., LaFleur, B., Spraker, M. B., Seo, Y. D., Smythe, K. S., Campbell, J. S., Pierce, R. H., Zhang, Y., He, Q., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-4239 · Cited by 49
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“Data from three clinical studies show that the presence of B-cell clusters in TLS predicts a signi fi cant response to anti – PD-1 therapy (4 – 6).”
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Preventive effect of tertiary lymphoid structures on lymph node metastasis of lung adenocarcinoma
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The anti-cancer immune response in breast cancer: current and emerging biomarkers and treatments
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“There are some existing methods to determine the positive threshold:”
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The epigenetic hallmarks of immune cells in cancer
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“Antitumor B cells are primarily observed in tertiary lymphoid structures (TLS) where they are associated with DCs to form germinal centers and surrounded by T cells [141].”
Analysis of DNA methylation patterns in the tumor immune microenvironment of metastatic melanoma
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“Recently, the existence and importance of tertiary lymphoid structures (TLS) in the melanoma tumors have been reported along with their close relationship with prognosis and response to immunotherapeutic treatments (Cabrita et al., 2020; Helmink et al., 2020).”
BackgroundExtracellular Vesicles Mediate B Cell Immune Response and Are a Potential Target for Cancer Therapy
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“Specifically, mass cytometry revealed memory B cells to be enriched in the tumor of responders [28].”
BackgroundHe, W., Zhang, D., Liu, H., Chen, T., Xie, J., Peng, L., Zheng, X., Xu, B., Li, Q., & Jiang, J. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00980 · Cited by 47
Droste, M., Tertel, T., Jeruschke, S., Dittrich, R., Kontopoulou, E., Walkenfort, B., Börger, V., Hoyer, P. F., Büscher, A. K., Thakur, B. K., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212436 · Cited by 46
“Moreover, a novel direct stochastic optical reconstruction (dSTORM) device, the Nanoimager, also allows single sEV analyses [49].”
MethodFrigola, J., Navarro, A., Carbonell, C., Callejo, A., Iranzo, P., Cedrés, S., Martínez‐Martí, A., Pardo, N., Gonzalez, N. S., Martinez, D., et al. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12891 · Cited by 47
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Cancer Cell Phenotype Plasticity as a Driver of Immune Escape in Melanoma
Benboubker, V., Boivin, F., Dalle, S., & Caramel, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.873116 · Cited by 51
Bugatti, M., Bergamini, M., Missale, F., Monti, M., Ardighieri, L., Pezzali, I., Picinoli, S., Caronni, N., Missolo-Koussou, Y., Helft, J., et al. (2022) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-22-0271 · Cited by 45
Taylor, J., Gandhi, A., Gray, E. S., & Zaenker, P. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.991433 · Cited by 47
Petroni, G., Pillozzi, S., & Antonuzzo, L. (2024) · Cancer Research · doi:10.1158/0008-5472.can-23-3325 · Cited by 52
“The presence of TLS-associated TIL-Bs has been associated with extended overall survival in patients with melanoma, soft-tissue sarcomas, renal cell carcinoma, and NSCLC, treated with ICIs(5,6,8 – 10),thussuggestingarolefor TLSandhumoralimmunity in mediating ICI responses in these settings.”
BackgroundInfiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding
Gao, J., Gu, D., Yang, K., Zhang, J., Lin, Q., Yuan, W., Xu, Z., Dixit, D., Gimple, R. C., You, H., et al. (2025) · Cancer Cell · doi:10.1016/j.ccell.2024.12.006 · Cited by 47
Self-citationImmunocytes in the tumor microenvironment: recent updates and interconnections
Yu, J., Fu, L., Wu, R., Che, L., Liu, G., Ran, Q., Xia, Z., Liang, X., & Zhao, G. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1517959 · Cited by 52
König, D., & Laubli, H. P. (2020) · Pharmacology · doi:10.1159/000509081 · Cited by 49
B cells in lung cancer—not just a bystander cell: a literature review
Leong, T. L., & Bryant, V. L. (2021) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-788 · Cited by 46
“respectively demonstrated that the presence of B cells in TLS in the tumor before treatment was associated with increased chance of response to immunotherapy (80,81).”
BackgroundB cell heterogeneity, plasticity, and functional diversity in cancer microenvironments
Yuan, W., Huang, C.-X., Xiao, C., Chen, D., Shan, H., He, H., & Kuang, D. (2021) · Oncogene · doi:10.1038/s41388-021-01918-y · Cited by 46
“Mass cytometry further confirms the mature status and immunoglobulin class-switched phenotypes of these cells [84].”
BackgroundYang, B., Zhang, Z., Chen, X., Wang, X.-Y., Qin, S., Du, L., Yang, C., Zhu, L., Sun, W., Zhu, Y., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci153454 · Cited by 49
“Recent investigations of immune profiles in the TME have identified tertiary lymphoid structure (TLS) as favorable prognostic markers in several cancer types, and B cells have been shown to be one of the major initiators of the TLS formation (9-12).”
BackgroundSelf-citationWu, Y., Wen, H., Bernstein, Z. J., Hainline, K. M., Blakney, T. S., Congdon, K. L., Snyder, D. J., Sampson, J. H., Sanchez-Perez, L. A., & Collier, J. H. (2022) · Science Advances · doi:10.1126/sciadv.abm7833 · Cited by 48
Jiang, J., & Ying, H. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02457-4 · Cited by 47
“which B cells cooperate with T cells in maturation and activation [26, 27].”
BackgroundExosomal lncRNA HOTAIR induces PDL1+ B cells to impede anti-tumor immunity in colorectal cancer
Xie, Z., Xia, J., Jiao, M., Zhao, P., Wang, Z., Lin, S., Xing, Y., Li, Y., Zhou, L., Zhong, Z., et al. (2023) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2023.01.005 · Cited by 46
Self-citationTrial watch: Toll-like receptor ligands in cancer therapy
Naour, J. L., & Kroemer, G. (2023) · OncoImmunology · doi:10.1080/2162402x.2023.2180237 · Cited by 45
“Enrichment of tertiary lymphoid structure, memory B cells, and plasma cells is a positive prognostic factor in for various solid tumors.(57,58) Additionally, activation of TLR9 in B cells leads to the expression of co-stimulatory molecules with enhanced cross-presentation allowing for activation and proliferation of T…”
BackgroundChen, X., Xu, H., Chen, X., Xu, T., Tian, Y., Wang, D., Guo, F., Wang, K., Jin, G., Li, X., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01773-9 · Cited by 49
“32 – 34 This fi nding may underpin the favorable ef fi cacy of the combination therapy.”
BackgroundReschke, R., Enk, A. H., & Hassel, J. C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126532 · Cited by 51
“CXCL13 and TLS formations in tumors are correlated with the response to immunotherapy in melanoma and other tumors [36,37].”
BackgroundLong, S., Li, M., Chen, J., Zhong, L., Abudulimu, A., Zhou, L., Liu, W., Pan, D., Dai, G., Fu, K., et al. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-009879 · Cited by 45
Self-citationPradhan, M., Chocry, M., Gibbons, D. L., Sepesi, B., & Cascone, T. (2021) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-573 · Cited by 44
“In a recent work using tumor specimens from patients with high-risk resectable melanoma and metastatic renal cell carcinoma (RCC) treated with presurgical ICIs, Helmnik and colleagues (72) discovered that B cell signatures were enriched in tumors of patients who responded to treatment when compared to nonresponders.”
BackgroundGong, L., Kwong, D. L., Dai, W., Wu, P., Wang, Y., Lee, A. W. M., & Guan, X. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.744889 · Cited by 45
“Increased B cell density in the TME facilitates the establishment of TLSs and promotes responsiveness to PD-1/ CTLA4 immunotherapy in melanoma (80, 81).”
Backgroundvan Akkooi, A. C. J., Hieken, T. J., Burton, E. M., Ariyan, C. E., Ascierto, P. A., Asero, S. V. M. A., Blank, C. U., Block, M. S., Boland, G. M., Caracò, C., et al. (2022) · Annals of Surgical Oncology · doi:10.1245/s10434-021-11236-y · Cited by 47
Self-citationThe Tumor Immune Landscape and Architecture of Tertiary Lymphoid Structures in Urothelial Cancer
van Dijk, N., Gil-Jimenez, A., Siliņa, K., van Montfoort, M. L., Einerhand, S. M. H., Jonkman, L., Voskuilen, C. S., Peters, D. D. G. C., Sanders, J., Lubeck, Y., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.793964 · Cited by 44
Zou, R., Jiang, Q., Jin, T., Chen, M., Yao, L., & Ding, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.956224 · Cited by 44
New opportunities for immunomodulation of the tumour microenvironment using chemical tools
Su, J., Li, W., & Li, Y. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00486k · Cited by 44
Zhu, P., #x2019, #x2019, Lu, H., Wang, M., Chen, K., Chen, Z., & Yang, L. (2023) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2022.0491 · Cited by 44
Cheng, C., Nguyen, T. T., Tang, M., Wang, X., Jiang, C., Liu, Y., Gorlov, I. P., Gorlova, O. Y., Iafrate, J., Lanuti, M. D., et al. (2023) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2023.04.022 · Cited by 43
Targeting molecular pathways to control immune checkpoint inhibitor toxicities
Reschke, R., Sullivan, R. J., Lipson, E. J., Enk, A. H., Gajewski, T. F., & Hassel, J. C. (2024) · Trends in Immunology · doi:10.1016/j.it.2024.11.014 · Cited by 44
Ho, A. Y., Wright, J. L., Blitzblau, R. C., Mutter, R. W., Duda, D. G., Norton, L., Bardia, A., Spring, L. M., Isakoff, S. J., Chen, J. H., et al. (2020) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2020.05.011 · Cited by 45
Protein Arginine Methylation: An Emerging Modification in Cancer Immunity and Immunotherapy
Dai, W., Zhang, J., Li, S., He, F., Liu, Q., Gong, J., Yang, Z., Gong, Y. Q., Tang, F., Wang, Z., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.865964 · Cited by 49
Intratumoral immunotherapy relies on B and T cell collaboration
Sagiv-Barfi, I., Czerwinski, D. K., Shree, T., Lohmeyer, J. J. K., & Levy, R. (2022) · Science Immunology · doi:10.1126/sciimmunol.abn5859 · Cited by 44
Advances in plant-derived natural products for antitumor immunotherapy
Yang, Y., Liu, Q., Shi, X., Zheng, Q., Chen, L., & Sun, Y. (2021) · Archives of Pharmacal Research · doi:10.1007/s12272-021-01355-1 · Cited by 45
Tumor and local lymphoid tissue interaction determines prognosis in high-grade serous ovarian cancer
Lu, H., Lou, H., Wengert, G., Paudel, R., Patel, N. R., Desai, S., Crum, B., Linton‐Reid, K., Chen, M., Li, D., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101092 · Cited by 43
Playoust, E., Remark, R., Vivier, É., & Milpied, P. (2023) · Cellular and Molecular Immunology · doi:10.1038/s41423-023-01060-7 · Cited by 44
“[31] revealed that Bmem cells were the most enriched B-cell subset in responder patient samples (51%), followed by PC (16.”
BackgroundMethodZhao, R., Li, J., Chen, B., Zhao, J., Hu, L., Huang, K., Chen, Q., Yao, J., Lin, G., Bao, L., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1289753 · Cited by 43
“TLS, tertiary lymphoid structure; It-TLS group, Intratumoral TLS group; De-TLS group, Desertic TLS group. and was associated with good patient prognosis (10, 27), similar conclusions have been obtained in most tumors (28 – 30).”
BackgroundResultAdditive Role of Immune System Infiltration and Angiogenesis in Uveal Melanoma Progression
García‐Mulero, S., Alonso, M. H., del Carpio, L. P., Pamplona, R. S., & Piulats, J. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052669 · Cited by 44
Singh, S., Long, J. P., Tchakarov, A. S., Dong, Y., Yee, C., & Lin, J. S. (2022) · JCI Insight · doi:10.1172/jci.insight.165108 · Cited by 49
“The total number of TLS detected per case was normalized to the total amount of biopsied renal cortex (mm2) per case (34, 48).”
MethodResultLow KRT15 expression is associated with poor prognosis in patients with breast invasive carcinoma
Zhong, P., Shu, R., Wu, H., Liu, Z., Shen, X., & Hu, Y. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.9736 · Cited by 42
Beyes, S., Bediaga, N. G., & Zippo, A. (2021) · Cancers · doi:10.3390/cancers13194969 · Cited by 44
“have demonstrated an association between the responsiveness to immune checkpoint inhibitors and the presence of tertiary lymphoid structures and clonal B cell expansion in melanoma [131].”
BackgroundEmerging Biomaterials Imaging Antitumor Immune Response
Ma, X., Zhang, M., Wang, J., Zhang, T., Xue, P., Kang, Y., Sun, Z., & Xu, Z. (2022) · Advanced Materials · doi:10.1002/adma.202204034 · Cited by 42
Activated B cells suppress T-cell function through metabolic competition
Imahashi, N., Başar, R., Huang, Y., Wang, F., Baran, N., Banerjee, P. P., Lu, J., Cortes, A. K. N., Uprety, N., Ensley, E. L., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-005644 · Cited by 42
Self-citationTertiary Lymphoid Structure Raises Survival and Immunotherapy in HPV − HNSCC
Li, H., Zhu, S., Zhou, J., Chen, D.-R., Liu, J., Zz, W., Wang, W., Zhang, M.-J., & Sun, Z. (2023) · Journal of Dental Research · doi:10.1177/00220345231151685 · Cited by 43
“The presence of TLSs in tumors has been shown to be a prognostic and predictive marker in multiple tumor types, suggesting a crucial role of TLS in the antitumor immune response and ICB therapy (Cabrita et al. 2020; Helmink et al. 2020; Petitprez et al. 2020; Vanhersecke et al. 2021).”
BackgroundB cells and the coordination of immune checkpoint inhibitor response in patients with solid tumors
Flippot, R., Teixeira, M., Rey-Cárdenas, M., Carril-Ajuria, L., Rainho, L., Naoun, N., Jouniaux, J.-M., Boselli, L., Naigeon, M., Danlos, F., et al. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2023-008636 · Cited by 47
“40 48 49 53–56”
BackgroundInfluentialZhang, S., Deshpande, A. M., Verma, B. K., Wang, H., Mi, H., Yuan, L., Ho, W. J., Jaffee, E. M., Zhu, Q., Anders, R. A., et al. (2024) · Cancer Research · doi:10.1158/0008-5472.can-24-0943 · Cited by 47
Self-citationSchooten, T. S. G.-V., Fernandez, R. F., van Grieken, N. C. T., Bos, E. N., Seidel, J., Saris, J., Martínez‐Ciarpaglini, C., Fleitas, T. C., Thommen, D. S., de Gruijl, T. D., et al. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-009243 · Cited by 42
Burgers, F. H., van der Mijn, J. C., Seijkens, T. T. P., Jedema, I., Bex, A., & Haanen, J. B. A. G. (2025) · Nature Reviews Nephrology · doi:10.1038/s41581-025-00983-w · Cited by 49
Foster, C. C., Fleming, G. F., Karrison, T. G., Liao, C., Desai, A. V., Moroney, J. W., Ratain, M. J., Nanda, R., Polite, B. N., Hahn, O. M., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0810 · Cited by 41
“Related gene expression analyses suggest a molecular basis for these observations including SBRTinduced expression of genetic pathways governing B-cell development, antigen presentation, and dendritic cell maturation (22, 23) as well as SBRT-induced suppression of pathways intertwinedwith the cell cycle, histone modif…”
BackgroundImmune Cycle‐Based Strategies for Cancer Immunotherapy
Li, Y., Liu, X., Zhang, X., Pan, W., Li, N., & Tang, B. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202107540 · Cited by 42
Xu, W., Ma, C., Liu, W., Anwaier, A., Tian, X., Shi, G., Qu, Y., Wei, S., Zhang, H., & Ye, D. (2022) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-021-03123-y · Cited by 42
Self-citationHummelink, K., van der Noort, V., Muller, M., Schouten, R. D., Lalezari, F., Peters, D. D. G. C., Theelen, W. S. M. E., Koelzer, V. H., Mertz, K. D., Zippelius, A., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-0992 · Cited by 42
Self-citationTertiary lymphoid structure patterns predicted anti-PD1 therapeutic responses in gastric cancer
Jiang, Q., Tian, C., Wu, H., Min, L., Chen, H., Chen, L., Liu, F., & Sun, Y. (2022) · Chinese Journal of Cancer Research · doi:10.21147/j.issn.1000-9604.2022.04.05 · Cited by 44
CXCL13 shapes tertiary lymphoid structures and promotes response to immunotherapy in bladder cancer
Rouanne, M., Arpaia, N., & Marabelle, A. (2021) · European Journal of Cancer · doi:10.1016/j.ejca.2021.03.054 · Cited by 42
Boisson, A., Noel, G. L., Saiselet, M., Vitória, J. R., Thomas, N., Fontsa, M. L., Sofronii, D., Naveaux, C., Duvillier, H., Craciun, L., et al. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.673042 · Cited by 43
Xu, X., Guo, Q., Cui, C., Lin, Y., Zhang, L. J., Ding, X., Li, Q., Wang, M., Yang, W., Kong, Y., et al. (2022) · Communications Medicine · doi:10.1038/s43856-022-00197-2 · Cited by 46
Immunotherapy in Sarcoma: Current Data and Promising Strategies
Wood, G. E., Meyer, C. F., Petitprez, F., & D’Angelo, S. P. (2024) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_432234 · Cited by 47
Self-citationMature tertiary lymphoid structures: important contributors to anti-tumor immune efficacy
Bao, X., Lin, X., Xie, M., Yao, J., Song, J., Ma, X., Zhang, X., Zhang, Y., Liu, Y., Han, W., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1413067 · Cited by 45
“The heightened presence of B-cell memory features and PCs within mature TLS is associated with improved prognostic outcomes in cancer treatment, underscoring a signi fi cant humoral immune role for B cells within mature TLS (33, 51).”
BackgroundResultInfluentialCakmak, P., Lun, J. H., Singh, A., Macas, J., Schupp, J., Schuck, J., Mahmoud, Z., Köhler, M. I., Starzetz, T., Burger, M. C., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.09.018 · Cited by 42
CRISPR screen in mechanism and target discovery for cancer immunotherapy
Liu, D., Zhao, X., Tang, A., Xu, X., Liu, S., Zha, L., Ma, W., Zheng, J., & Shi, M. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188378 · Cited by 44
Yang, H., Hall, S. R. R., Sun, B., Zhao, L., Gao, Y., Schmid, R. A., Tan, S. T., Peng, R., & Yao, F. (2021) · Cancers · doi:10.3390/cancers13071561 · Cited by 43
“Regarding B-cell infiltrates, which have been shown to play a role in promoting the anti-tumor immune response [24,47], interestingly, MPM tumors harboring LATS1/2 rather than NF2 display enriched plasma B-cell signature (Figure S6).”
BackgroundInfluentialBreast cancer resistance mechanisms: challenges to immunotherapy
Hanna, A., & Balko, J. M. (2021) · Breast Cancer Research and Treatment · doi:10.1007/s10549-021-06337-x · Cited by 45
Jia, L., Wang, T., Zhao, Y., Zhang, S., Ba, T., Kuai, X., Wang, B., Zhang, N., Zhao, W., Yang, Z., et al. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1969767 · Cited by 42
“Immune-related lymphoid tissues (TLSs) include MALT and skin-related lymphoid tissue.(11) MALT can be found in various submucosal membrane sites of the body, such as the”
BackgroundSelf-citationXia, L., Guo, L., Kang, J. U., Yang, Y., Yao, Y., Xia, W., Sun, R., Zhang, S., Li, W., Gao, Y.-E., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.759217 · Cited by 40
Self-citationSun, Y., Zhang, Y., Ren, S., Li, X., Yang, P., Zhu, J., Lin, L., Wang, Z., & Jia, Y. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106454 · Cited by 41
Cai, J., Ji, Z., Wu, J., Chen, L., Zheng, D., Chen, Y., Zhang, X., Xie, W., Huang, J., Chen, M., et al. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.949314 · Cited by 40
Rochais, M. L., Hémon, P., Ben-guigui, D., Garaud, S., Dantec, C. L., Pers, J., Cornec, D., & Uguen, A. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1147480 · Cited by 43
T follicular helper cells in cancer, tertiary lymphoid structures, and beyond
Cui, C., Craft, J. E., & Joshi, N. S. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101797 · Cited by 42
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
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