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.
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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.
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.
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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
“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.
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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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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.
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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.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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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.
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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.
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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.
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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.
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.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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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.
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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.
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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.
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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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“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
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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
Items 901–1,000 of 1,004
Zheng, K. C., Gao, L., Hao, J., Zou, X., & Hu, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.972227 · Cited by 23
“Prev ious whole -exome sequenc ing (WES) and transcriptome sequencing of tumors identified several factors associated with ICB outcomes, such as high T/low myeloid cell infiltration (7), high B-cell (8)/CD4 memory T cell abundance (9), elevated PD-L1 expression (10), high tumor mutational burden (TMB) (11), and high s…”
An, Y., Sun, J., Xu, M., Xu, J., Ma, S.-Y., Liu, C., Liu, Z., Wang, S., & Xia, Q. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1049884 · Cited by 24
“In addition, studies have revealed that B cells and TLSs are tightly associated with the response to immunotherapy (14), and the presence of TLSs is a predictive factor for the response to ICB therapy in sarcoma and melanoma (15, 16).”
BackgroundResultLiu, W., Tai, C., Liu, X., & Pastan, I. H. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2214928119 · Cited by 22
“Both increased B cells and CD8 + T cells are favorable prognostic markers for mesothelioma patients (31–33), and the presence of TLSs is a portent of improved responsiveness to immunotherapy in many kinds of cancers (melanoma, sarcoma, and renal cell carcinoma) (24, 34, 35).”
Self-citationLi, K., Ji, J., Li, S., Yang, M. G., Che, Y., Zhu, X., Zhang, Y., Wang, M., Fang, Z., Luo, L., et al. (2023) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.28900 · Cited by 22
“9 In most solid tumors, clinical trials have shown that the presence of TLSs is associated with good prognosis and response to immunotherapy, and this may become a new potential biomarker related to cancer prognosis.”
BackgroundNeoadjuvant Immunotherapy for Localized Pancreatic Cancer: Challenges and Early Results
Chick, R. C., Gunderson, A. J., Rahman, S., & Cloyd, J. M. (2023) · Cancers · doi:10.3390/cancers15153967 · Cited by 22
“intratumoral tertiary lymphoid aggregates (TLA), a finding thought to be attributable to GVAX and associated with response to immunotherapy in other cancers [37] and survival in PDAC [13,38].”
BackgroundChen, S., Yu, R., Hong, X., Zhang, P., Guo, Y., Cai, J., & Hou, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241612890 · Cited by 23
Li, R., Nocera, L., Rose, K. M., Raggi, D., Naidu, S. U., Mercinelli, C., Cigliola, A., Tateo, V., Patanè, D. A., Grass, G. D., et al. (2024) · European Urology Oncology · doi:10.1016/j.euo.2023.12.008 · Cited by 21
Lee, J., Kim, D., Kong, J., Ha, D., Kim, I., Park, M., Lee, K., Im, S., & Kim, S. (2024) · Science Advances · doi:10.1126/sciadv.adj0785 · Cited by 23
“CXCL13, also called B cell attracting chemokine-1, recruits B cells to build a TLS in the TIME, which plays a major role in response to ICIs ( 47 , 48 ).”
BackgroundSelf-citationTian, J., & Quek, C. Y. J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084243 · Cited by 23
“Their clinical values in promoting immunotherapy response and improving patient survival outcomes have been suggested in recent studies [60,116].”
ResultClinical correlates for immune checkpoint therapy: significance for CNS malignancies
Ratnam, N. M., Frederico, S. C., Gonzalez, J., & Gilbert, M. R. (2020) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdaa161 · Cited by 22
López‐Janeiro, Á., Wong, E. M., Jiménez‐Sánchez, D., Ortíz-de-Solórzano, C., Lozano, M. D., Teijeira, Á., Schalper, K. A., Melero, I., & de Andrea, C. E. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2023-008589 · Cited by 23
“70 71 Systematic spatial mapping of various cell types in a nonrandom fashion is the basis of cellular neighborhood analysis.”
Koedijk, J. B., van der Werf, I. M., Penter, L., Vermeulen, M. A., Barneh, F., Perzolli, A., Meesters, J. I., Metselaar, D. S., Margaritis, T., Fiocco, M. F., et al. (2024) · Leukemia · doi:10.1038/s41375-024-02381-w · Cited by 25
Chung, S., Yeh, Y., Huang, C.-J., Chiang, N.-J., Hsu, D. S., Chan, M., Lu, M.-L., Hsu, T.-S., Hung, Y.-P., Yeh, C., et al. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-010173 · Cited by 21
Exploring effects of gut microbiota on tertiary lymphoid structure formation for tumor immunotherapy
Liu, Y., Li, F., Wang, J., & Yang, R. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1518779 · Cited by 22
Cui, M., Zhou, M., Zhou, L., Zhou, G., & Liu, Y. (2025) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2025.189312 · Cited by 21
Multiplex imaging analysis of the tumor immune microenvironment for guiding precision immunotherapy
Liu, F., Li, G., Zheng, Y., Liu, Y., & Liu, K. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1617906 · Cited by 24
“Patients exhibiting these immune “ hotspots ”— rich in activated immune cells, including B cells, dendritic cells, and CD8 + T cells — typically experience better clinical outcomes and sustained therapeutic responses (42).”
CRATER tumor niches facilitate CD8+ T cell engagement and correspond with immunotherapy success
Ludin, A., Stirtz, G. L., Tal, A., Nirmal, A. J., Pfaff, K. L., Manos, M. P., Besson, N. R., Eskndir, N., Porter, B. A., Jones, S. M., et al. (2025) · Cell · doi:10.1016/j.cell.2025.09.021 · Cited by 22
CXCL13-producing PD-1 hi CXCR5 − helper T cells in chronic inflammation
Yoshitomi, H. (2020) · Immunological Medicine · doi:10.1080/25785826.2020.1781998 · Cited by 22
Reticker-Flynn, N. E., & Engleman, E. G. (2020) · eLife · doi:10.7554/elife.53839 · Cited by 23
“While investigations into adaptive immune responses to tumors have long been a major focus of tumor immunologists, the recent successes of immune checkpoint blockade (ICB) and engineered chimeric antigen receptor T cells (CAR-T cells) have stimulated a renewed interest in understanding T cell interactions with tumors.”
MethodInfluentialThe Role of B Cells in Head and Neck Cancer
Gavrielatou, N., Vathiotis, I. A., Economopoulou, P., & Psyrri, A. K. (2021) · Cancers · doi:10.3390/cancers13215383 · Cited by 21
“metastatic renal cell carcinoma and advanced stage melanoma are associated with response to immune checkpoint blockade (ICB) treatment [56].”
BackgroundLiu, W., Wang, X., Feng, X., Yu, J., Liu, X., Jia, X., Zhang, H., Wu, H., Wang, C., Wu, J., et al. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.215661 · Cited by 21
Self-citationLi, J., Nie, Y., Jia, W., Wu, W., Song, W., & Li, Y. (2022) · Cancers · doi:10.3390/cancers14205157 · Cited by 21
“Tertiary lymphoid structures (TLSs) are newly discovered immune structures formed by the aggregation of lymphocytes in patients with chronic infections, immune diseases and tumours, which have the ability to initiate immune responses [10].”
BackgroundLi, J., Chen, Z., Chen, Y., Zhao, J., He, M., Li, X., Zhang, L., Dong, B., Zhang, X.-T., Tang, L., et al. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2022.1059874 · Cited by 21
“Previous studies have reported that on-treated tumor samples of patients with effective ICI response showed increased immune cell abundance and a low percentage of tumor cells (20, 21).”
BackgroundResultZhao, M., Chen, S., Li, C., Du, Y., & Li, P. (2023) · Cancers · doi:10.3390/cancers15030600 · Cited by 23
High-multiplex tissue imaging in routine pathology—are we there yet?
Einhaus, J. F., Rochwarger, A., Mattern, S., Gaudilliere, B. L., & Schürch, C. M. (2023) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-023-03509-6 · Cited by 23
Modulation of T cell function and survival by the tumor microenvironment
Mani, N. L., Andrews, D., & Obeng, R. C. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1191774 · Cited by 22
Anderson, K. G., Braun, D. A., Buqué, A., Gitto, S. B., Guerriero, J. L., Horton, B. L., Keenan, B. P., Kim, T. S., Overacre-Delgoffe, A. E., Ruella, M., et al. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-006533 · Cited by 22
“18 Inflamed tumors may also exhibit high levels of regulatory immune cells, such as T reg , as a compensatory response to a robust endogenous antitumor immunity, and retain responsiveness to immunotherapy despite the presence of inhibitory cells.”
Plasma cell signatures predict prognosis and treatment efficacy for lung adenocarcinoma
Shu, L., Tang, J., Liu, S., & Tao, Y. (2023) · Cellular Oncology · doi:10.1007/s13402-023-00883-w · Cited by 21
Biomarkers and experimental models for cancer immunology investigation
Xu, H., Jia, Z., Liu, F., Li, J., Huang, Y., Jiang, Y., Pu, P., Shang, T., Tang, P., Zhou, Y., et al. (2023) · MedComm · doi:10.1002/mco2.437 · Cited by 21
“67 The coexistence of B cells and T cells facilitated the formation of TLS, served a curial role in TME formation in melanoma, and led to an improved prognosis after cancer immunotherapy.”
BackgroundHeterogeneity of tertiary lymphoid structures in cancer
You, X., Koop, K., & Weigert, A. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1286850 · Cited by 21
“Although growing evidence suggests an important role of B cells in anti-tumor immunity and immunotherapy (109 – 111), the role of B cells in TLS towards clinical relevance is still understudied.”
BackgroundMethodGong, W., Zhang, S., Tian, X., Chen, W., He, Y., Chen, L., Ding, T., Ren, P., Shi, L., Wu, Q., et al. (2024) · Hepatology International · doi:10.1007/s12072-024-10694-2 · Cited by 21
“Recent studies have successfully demonstrated the correlation between TLSs and immunotherapy in melanoma and sarcoma, indicating that the formation of TLSs is associated with a favourable response to ICI treatment [11, 12].”
BackgroundSelf-citationSaux, O. L., Ardin, M., Berthet, J., Ghamry-Barrin, S., Bourhis, M., Cinier, J., Lounici, Y., Treilleux, I., Just, P., Bataillon, G., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-47000-5 · Cited by 21
“A higher fraction of patients treated with NACT+P displayed increased expression of the CD8 + T cell gene signature (MCP-counter) post-treatment (71%, 95% CI [52 – 85] vs 52%, 95% CI [30 – 74]) (Fig.”
B cells and TLSs facilitate a response to ICI
Romero, D. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0338-6 · Cited by 21
Guo, Y., Dong, X., Jin, J., & He, Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.663001 · Cited by 24
Shu, D. H., Ho, W. J., Kagohara, L. T., Girgis, A. A., Shin, S. M., Danilova, L., Lee, J. W., Sidiropoulos, D. N., Mitchell, S., Munjal, K., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.16.562104 · Cited by 21
Self-citationMattiuz, R., Boumelha, J., Hamon, P., Bérichel, J. L., Vaidya, A. B., Soong, B. Y., Halász, L., Radkevich, E., Kim, H. M., Park, M. D., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.27.628014 · Cited by 21
Self-citationOuyang, W., Peng, Q., Lai, Z., Huang, H., Huang, Z., Xie, X., Lin, R., Wang, Z., Yao, H., & Yu, Y. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e27151 · Cited by 20
“Historically, this chemokine has been recognized for its role in orchestrating secondary lymphoid structures and recruiting B cells [34,35].”
BackgroundSiddiqui, B. A., Palaskas, N. L., Basu, S., Dai, Y., He, Z., Yadav, S. S., Allison, J. P., Sheth, R. A., Tummala, S., Buja, L. M., et al. (2024) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-24-0011 · Cited by 21
Self-citationYoshikawa, T., & Yanagita, M. (2024) · American Journal Of Pathology · doi:10.1016/j.ajpath.2024.07.008 · Cited by 22
“34 Additionally, tumors harboring mature TLSs with germinal centers were associated with the enrichment of multiple myeloma oncogene 1 (MUM1) þ IgG þ plasma cell in fi ltrates in tumors and frequency of IgG-labeled tumor cells, suggesting the production of antitumor antibodies by plasma cells…”
Priming immunity via herbal components and their nanomedicines for the treatment of cancer
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“Their presence improves the prognosis of different cancer types, including breast cancer, melanoma, renal cell carcinoma, colorectal cancer (CRC), hepatocellular carcinoma (HCC), and head and neck squamous cell carcinoma [212–215] .”
Lehmann, J. M., Thelen, M., Kreer, C., Schran, S., Garcia-Marquez, M. A., Cisic, I., Siepmann, K., Hagen, E. M., Eckel, H. N. C., Lohneis, P., et al. (2024) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-24-0299 · Cited by 20
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“T cells within TLSs exhibit increased activation markers compared with other tumor-resident T cells in melanoma 34 .”
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McKenzie, M. E., Irac, S. E., Chen, Z., Moradi, A., Jenner, A. L., Nguyen, Q. H., & Rashidieh, B. (2026) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2026.01.002 · Cited by 24
Cancer ecosystems: A dynamic interplay across scales
Quail, D. F., & Joyce, J. A. (2026) · Cell · doi:10.1016/j.cell.2026.03.003 · Cited by 26
Multimodal predictors for precision immunotherapy
Roelofsen, L. M., Kaptein, P., & Thommen, D. S. (2022) · Immuno-Oncology Technology · doi:10.1016/j.iotech.2022.100071 · Cited by 19
“Accordingly, the induction of a downstream IFN-g -cell clones have been observed in responding patients.(67,92-94) As in most of these studies the on-treatment samples were collected a few weeks to months after treatment start, however, they have limited utility to study early dynamics of the induced response.”
BackgroundZheng, D., Zhang, Y., Xia, Y., & Fan, C. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.840410 · Cited by 20
“The infiltrated B cells played role in the response to immune checkpoint blockade treatment (32).”
BackgroundYu, J.-S., Huang, W., Zhang, Y., Chen, J., Li, J., Fu, H., Wei, Z.-W., & He, Y. (2022) · Neoplasma · doi:10.4149/neo_2022_220128n123 · Cited by 21
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“The transcriptome and proteomic analysis of ICB-treated melanoma and renal cell carcinoma cohorts revealed unique func‐ tional states of B cells in responders, which appeared more memory-like (Amaria et al., 2018; Helmink et al., 2020).”
BackgroundInfluentialSelf-citationGiatromanolaki, A. N., Chatzipantelis, P., Contrafouris, C., & Koukourakis, M. I. (2022) · Cancer Investigation · doi:10.1080/07357907.2022.2136684 · Cited by 20
“An interesting study, however, supports this hypothesis (29).”
ResultWare, M. B., Wolfarth, A. A., Goon, J. B., Ezeanya, U. I., Dhar, S., Ferrando‐Martínez, S., & Lee, B. H. (2022) · Journal of Immunotherapy and Precision Oncology · doi:10.36401/jipo-22-10 · Cited by 20
“Further, an increasing body of evidence point to TLSs as key mediators of response to immunotherapy.([5,14,15,67,89,90]) The induction of TLSs has been associated with inflammatory reactions such as vaccination, viral infection, arthritis, Sjogren’s syndrome, and insulitis.”
BackgroundBarb, A. C., Fenesan, M. P., Pirtea, M., Margan, M.-M., Tomescu, L. C., Melnic, E., & Cîmpean, A. M. (2023) · Cells · doi:10.3390/cells12081176 · Cited by 20
“The novelty of the research topic as well as the extremely limited data regarding the impact of TLSs on BC prognosis and response to therapy is supported by the existence of a limited number of papers in the field [10].”
BackgroundHui, Z., Ren, Y., Zhang, D., Chen, Y., Yu, W., Cao, J., Liu, L., Wang, T., Xiao, S., Zheng, L., et al. (2023) · npj Precision Oncology · doi:10.1038/s41698-023-00384-x · Cited by 21
“Collectively, these fi ndings highlighted the potential utility of these subpopulations in predicting outcomes and suggested that B cells and CD8 + T cells may be key executors in mediating anti-PD-1-based therapies 29,32 .”
InfluentialHouel, A., Foloppe, J., & Dieu‐Nosjean, M. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101796 · Cited by 20
Boll, L. M., Perera‐Bel, J., Rodríguez‐Vida, A., Arpí, O., Rovira, A., Juanpere-Rodero, N., de Oca, S. V. M., Hernández‐Llodrà, S., Lloreta, J., Albà, M. M., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-42495-2 · Cited by 21
“While a positive correlation between B cells and improved survival was suggested for different cancer types 51,52 , other studies reported B cell content not to be associated with response to anti-PD-1 in melanoma 53 tended to be lower in responders than non-responders.”
Of mice and lymphoid aggregates: modeling tertiary lymphoid structures in cancer
Vaccaro, A., van de Walle, T., Ramachandran, M., Essand, M., & Dimberg, A. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1275378 · Cited by 20
“TLS have been identi fi ed in numerous cancer types, and their correlation with extended survival and response to immunotherapy has been extensively explored (10, 11), establishing TLS as robust biomarkers with potential clinical utility in patient strati fi cation.”
BackgroundParticipation of B cell in immunotherapy of cancer
Chandnani, N., Gupta, I., Mandal, A., & Sarkar, K. (2024) · Pathology - Research and Practice · doi:10.1016/j.prp.2024.155169 · Cited by 20
Prospects of Synergy: Local Interventions and CAR T Cell Therapy in Solid Tumors
Holtermann, A., Gislon, M., Angele, M. K., Subklewe, M. S., von Bergwelt‐Baildon, M., Lauber, K., & Kobold, S. (2024) · BioDrugs · doi:10.1007/s40259-024-00669-y · Cited by 21
B cell–based therapy produces antibodies that inhibit glioblastoma growth
Wang, S., Castro, B. A., Katz, J. L., Arrieta, V. A., Najem, H., Vazquez-Cervantes, G. I., Wan, H., Olson, I., Hou, D., Dapash, M., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci177384 · Cited by 20
Franco-Luzón, L., García‐Mulero, S., Pamplona, R. S., Melen, G. J., Ruano, D., Lassaletta, Á., Madero, L., González‐Murillo, Á., & Ramírez, M. R. (2020) · Cancers · doi:10.3390/cancers12051104 · Cited by 20
“The presence of the major immune cell populations also corresponded to the chemokine profiles responsible for their recruitment, as was the case with those related to B lymphocytes and dendritic cells at the time of disease stabilization [35,36].”
BackgroundCannon, A. C., Thompson, C. M., Maurer, H. C., Atri, P., Bhatia, R., West, S. C., Ghersi, D., Olive, K. P., Sushil Kumar, K., & Batra, S. K. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-1359 · Cited by 19
Next-Generation Immunotherapies to Improve Anticancer Immunity
Shi, Y., Tomczak, K. J., Li, J., Ochieng, J. K., Lee, Y., & Haymaker, C. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.566401 · Cited by 22
Non-canonical PD-1 signaling in cancer and its potential implications in clinic
Zha, H., Jiang, Y., Wang, X., Shang, J., Wang, N., Yu, L., Zhao, W., Li, Z., Zhang, X., Zhang, X., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001230 · Cited by 24
Deronic, A., Nilsson, A., Thagesson, M., Werchau, D., Smith, K. E., & Ellmark, P. (2021) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-021-02932-5 · Cited by 20
Sun, X., Lu, Y., Wu, J., Wen, Q., Li, Z., Tang, Y., Shi, Y., He, T., Liu, L., Huang, W., et al. (2023) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.123.318762 · Cited by 19
“14 In different diseases, their presences are associated with different outcomes and prognoses.”
BackgroundChen, Y., Wang, P., Hu, Y., Yuan, Y., Yang, Y., Shi, H., Hao, Q., Lin, Z., Tian, J., Zheng, Y., et al. (2024) · British Journal of Cancer · doi:10.1038/s41416-024-02805-5 · Cited by 19
Gorbokon, N., Wößner, N., Ahlburg, V., Plage, H., Hofbauer, S. L., Furlano, K., Weinberger, S., Bruch, P. G., Schallenberg, S., Roßner, F., et al. (2024) · The Journal of Pathology Clinical Research · doi:10.1002/2056-4538.70012 · Cited by 19
Ahn, W., Han, J.-H., Kim, N., Hwang, Y. H., Kim, W., Lee, Y., Lee, D. Y., Cheong, I. W., Han, K., Nam, G., et al. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123166 · Cited by 19
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Ruiz‐Torres, D. A., Bryan, M. E., Hirayama, S., Merkin, R. D., Luciani, E. G., Roberts, T. J., Patel, M. J., Park, J. C., Wirth, L. J., Sadow, P. M., et al. (2025) · OncoImmunology · doi:10.1080/2162402x.2025.2466308 · Cited by 19
“10,11,26,38 Interestingly, higher densities of CD20+ B cells and their physical interaction with CD8 T cells were associated with improved prognosis in treatment-naive HPV+OPSCC patients despite analyzing only ten representative low-powered visual fields per patient.”
Self-citationMultiple mechanisms and applications of tertiary lymphoid structures and immune checkpoint blockade
Li, Z., Liu, S., Liu, D., Yang, K., Xiong, J., & Fang, Z. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03318-6 · Cited by 21
Giri, S., Lamichhane, G., Pandey, J., Khadayat, R., Sindhu, K. C., Devkota, H. P., & Khadka, D. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26072923 · Cited by 22
“A recent study using bulk RNA sequencing has differentiated Bregs in tumors of responders and non-responders to ICIs, highlighting Bregs as potential therapeutic targets [31].”
Combinational therapeutic strategies to overcome resistance to immune checkpoint inhibitors
Al-Saafeen, B. H., Ali, B. R., & Elkord, E. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1546717 · Cited by 23
Immune organoid for cancer immunotherapy
Wang, X., Wang, W., & Sun, Z. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.04.031 · Cited by 21
“B cell-formed TLS in tumors play a crucial role in enhancing ICB therapy responses 58-60 .”
Milardi, G., Franceschini, B., Camisaschi, C., Puccio, S., Costa, G., Soldani, C., Uva, P., Cangelosi, D., Carriero, R., Lambroia, L., et al. (2025) · Gut · doi:10.1136/gutjnl-2025-334861 · Cited by 21
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Targeting angiogenesis: Lessons from 25 years of normalizing tumor vasculature
Subudhi, S., Lee, S., & Jain, R. K. (2026) · Cell · doi:10.1016/j.cell.2026.03.016 · Cited by 29
Pan-cancer spatial atlas of tertiary lymphoid structures
Cho, K. S., Liu, Y., Pei, G., Chen, J., Dai, Y., Liu, Y., Zhou, T., Bougoüin, A., Serrano, A., Wani, K., et al. (2026) · Science · doi:10.1126/science.adz2742 · Cited by 24
Self-citationHuman cutaneous B cells: what do we really know?
Lerman, I., Mitchell, D. C., & Richardson, C. T. (2021) · Annals of Translational Medicine · doi:10.21037/atm-20-5185 · Cited by 19
“…enrichment of B cell-related genes and activated T cell markers in ICB responders, but also reveals increased B cell receptor (BCR) diversity and clonal immunoglobulin heavy and light chain expression, supporting a critical role for B cells in anti-melanoma immunity within the skin (23,24).”
Cutaneous Melanoma: Mutational Status and Potential Links to Tertiary Lymphoid Structure Formation
Salem, D., Chelvanambi, M., Storkus, W. J., & Fecek, R. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.629519 · Cited by 19
Wang, N., Zhou, X., Tang, F., Wang, X. B., & Zhu, X. (2021) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-021-03193-4 · Cited by 19
“To further verify this trend, we applied the MCP-counter and xCell algorithm to evaluate the immune infiltration level in HCC, respectively.”
MethodRapid Serial Immunoprofiling of the Tumor Immune Microenvironment by Fine Needle Sampling
Oh, J., Carlson, J., Landeros, C., Lee, H., Ferguson, S. W., Faquin, W. C., Clark, J. R., Pittet, M. J., Pai, S. I., & Weissleder, R. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-1252 · Cited by 19
Semaphorins as Potential Immune Therapeutic Targets for Cancer
Jiang, J., Zhang, F., Wan, Y., Fang, K., Yan, Z., Ren, X., & Zhang, R. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.793805 · Cited by 21
“Wargo from the University of Texas MD Anderson Cancer Center found that B cells and tertiary lymphoid structures play an important role in tumor immunity (82).”
BackgroundEffect of immunotherapy on the immune microenvironment in advanced recurrent cervical cancer
Chen, R., Yang, W., Li, Y., Cheng, X., Nie, Y., Liu, D., & Wang, H. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.108630 · Cited by 19
A B‐cell or a key player? The different roles of B‐cells and antibodies in melanoma
Rodgers, C. B., Mustard, C. J., McLean, R. T., Hutchison, S., & Pritchard, A. L. (2022) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.13031 · Cited by 18
“Not all patients respond to ICB and a further subgroup develop resistance; research into what drives these responses has prompted a recent resurgence of interest in B- cells (Cabrita et al., 2020; Helmink et al., 2020; Petitprez et al., 2020).”
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B cells imprint adoptively transferred CD8 + T cells with enhanced tumor immunity
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Lee, J., Park, B. C., Jang, N. Y., Lee, S., Cho, Y. K., Sharma, P., Byun, S. W., Jeon, K., Jeon, Y., Park, U., et al. (2022) · Advanced Science · doi:10.1002/advs.202203842 · Cited by 19
Self-citationYazaki, S., Shimoi, T., Yoshida, M., Okuma, H. S., Arakaki, M., Saito, A., Kita, S., Yamamoto, K., Kojima, Y., Nishikawa, T., et al. (2022) · Breast Cancer Research and Treatment · doi:10.1007/s10549-022-06787-x · Cited by 22
The Tumor Microenvironment of Hepatocellular Carcinoma: Untying an Intricate Immunological Network
Volponi, C., Gazzillo, A., & Bonavita, E. (2022) · Cancers · doi:10.3390/cancers14246151 · Cited by 20
Seyhan, A. A., & Carini, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010041 · Cited by 22
Hoellwerth, M., Koelblinger, P., Lang, R., & Harrer, A. (2023) · Life · doi:10.3390/life13020553 · Cited by 21
“Melanoma patients responding to PD-1-immunotherapy showed a marked difference in the gene expression of B cell markers compared to non-responders [73].”
BackgroundDowns‐Canner, S., & Mittendorf, E. A. (2023) · Annals of Surgical Oncology · doi:10.1245/s10434-023-13267-z · Cited by 21
“Recommendations for a standardized approach to evaluation and treatment of irAEs was published by the Society for Immunotherapy of Cancer prior to the approval of neoadjuvant chemo-immunotherapy for TNBC.11 At our institutions, it is standard practice to monitor for irAEs, particularly thyroid dysfunction and adrenal…”
BackgroundInfluentialTissue- and liquid biopsy-based biomarkers for immunotherapy in breast cancer
Licata, L., Mariani, M., Rossari, F., Viale, G., Notini, G., Naldini, M. M., Bosi, C., Piras, M., Dugo, M., & Bianchini, G. (2023) · The Breast · doi:10.1016/j.breast.2023.03.014 · Cited by 19
Deep immune B and plasma cell repertoire in non-small cell lung cancer
Patel, A. J., Khan, N., Richter, A. G., Naidu, B. V., Drayson, M. T., & Middleton, G. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1198665 · Cited by 20
Numakura, K., Sekine, Y., Hatakeyama, S., Muto, Y., Sobu, R., Kobayashi, M., Sasagawa, H., Kashima, S., Yamamto, R., Nara, T., et al. (2023) · Cancer Medicine · doi:10.1002/cam4.6306 · Cited by 19
Xia, Z., Lü, C., Pan, C., Li, J., Li, J., Mao, Y., Sun, L., & Jiang, H. (2023) · BMC Medicine · doi:10.1186/s12916-023-02960-1 · Cited by 19
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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