{"doi":"10.3389/fimmu.2022.794684","title":"B Cells Are Required to Generate Optimal Anti-Melanoma Immunity in Response to Checkpoint Blockade","abstract":"Immunotherapies such as checkpoint blockade therapies are known to enhance anti-melanoma CD8 + T cell immunity, but only a fraction of patients treated with these therapies achieve durable immune response and disease control. It may be that CD8 + T cells need help from other immune cells to generate effective and long-lasting anti-tumor immunity or that CD8 + T cells alone are insufficient for complete tumor regression and cure. Melanoma contains significant numbers of B cells; however, the role of B cells in anti-melanoma immunity is controversial. In this study, B16 melanoma mouse models were used to determine the role of B cells in anti-melanoma immunity. C57BL/6 mice, B cell knockout (KO) C57BL/6 mice, anti-CD19, and anti-CXCL13 antibody-treated C57BL/6 mice were used to determine treatment efficacy and generation of tumor-specific CD8 + T cells in response to PD-L1 blockade alone or combination with TLR-7/8 activation. Whole transcriptome analysis was performed on the tumors from B cell depleted and WT mice, untreated or treated with anti-PD-L1. Both CD40-positive and CD40-negative B cells were isolated from tumors of TLR-7/8 agonist-treated wild-type mice and adoptively transferred into tumor-bearing B cell KO mice, which were treated with anti-PD-L1 and TLR-7/8 agonist. Therapeutic efficacy was determined in the presence of activated or inactivated B cells. Microarray analysis was performed on TLR-7/8-treated tumors to look for the B cell signatures. We found B cells were required to enhance the therapeutic efficacy of monotherapy with anti-PD-L1 antibody and combination therapy with anti-PD-L1 antibody plus TLR-7/8 agonist. However, B cells were not essential for anti-CTLA-4 antibody activity. Interestingly, CD40-positive but not CD40-negative B cells contributed to anti-melanoma immunity. In addition, melanoma patients’ TCGA data showed that the presence of B cell chemokine CXCL13 and B cells together with CD8 + T cells in tumors were strongly associated with improved overall survival. Our transcriptome data suggest that the absence of B cells enhances immune checkpoints expression in the tumors microenvironment. These results revealed the importance of B cells in the generation of effective anti-melanoma immunity in response to PD-1-PD-L1 blockade immunotherapy. Our findings may facilitate the design of more effective anti-melanoma immunotherapy.","journal":"Frontiers in Immunology","year":2022,"id":252632,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9471,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":254696,"name":"Jason Roszik","orcid":"0000-0002-4561-6170","position":1,"is_corresponding":false},{"id":418255,"name":"Neeraj K. Saini","orcid":"0000-0002-4087-025X","position":2,"is_corresponding":false},{"id":897159,"name":"Vipul Kumar Singh","orcid":"0000-0002-6897-6830","position":3,"is_corresponding":false},{"id":897823,"name":"Karishma Bavisi","orcid":null,"position":4,"is_corresponding":false},{"id":635002,"name":"Zhiqiang Wang","orcid":"0000-0003-4222-2026","position":5,"is_corresponding":false},{"id":873286,"name":"Long Vien","orcid":null,"position":6,"is_corresponding":false},{"id":654378,"name":"Zixi Yang","orcid":null,"position":7,"is_corresponding":false},{"id":525487,"name":"Suprateek Kundu","orcid":"0000-0002-1767-4875","position":8,"is_corresponding":false},{"id":390329,"name":"R. Eric Davis","orcid":"0000-0001-7311-0065","position":9,"is_corresponding":false},{"id":872613,"name":"Laura Bover","orcid":"0000-0003-2566-464X","position":10,"is_corresponding":false},{"id":90456,"name":"Adi Diab","orcid":"0000-0002-0153-0244","position":11,"is_corresponding":false},{"id":11096,"name":"Sattva S. Neelapu","orcid":"0000-0003-1045-4914","position":12,"is_corresponding":false},{"id":480145,"name":"Willem W. Overwijk","orcid":null,"position":13,"is_corresponding":false},{"id":18250,"name":"Kunal Rai","orcid":"0000-0003-2321-6894","position":14,"is_corresponding":false},{"id":897160,"name":"Manisha Singh","orcid":"0000-0003-1983-4921","position":15,"is_corresponding":false},{"id":897158,"name":"Shubhra Singh","orcid":"0000-0003-3854-8867","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":null,"created_at":"2026-07-19T00:24:50.819822Z","pmid":"35720386","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}