{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:22:16Z","timestamp":1792092136248,"version":"4.4.0"},"reference-count":53,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"unspecified","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["MBGI-22-158-01 (JY)"],"award-info":[{"award-number":["MBGI-22-158-01 (JY)"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["MBGI-23-1150374-01-MBG (CD)"],"award-info":[{"award-number":["MBGI-23-1150374-01-MBG (CD)"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["P20GM135004 (JY\/CD)"],"award-info":[{"award-number":["P20GM135004 (JY\/CD)"]}]},{"name":"NIH","award":["R01CA278941 (JY)"],"award-info":[{"award-number":["R01CA278941 (JY)"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2024,11,6]]},"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The role of B cells in antitumor immunity remains controversial, with studies suggesting the protumor and antitumor activity. This controversy may be due to the heterogeneity in B cell populations, as the balance among the subtypes may impact tumor progression. The immunosuppressive regulatory B cells (Breg) release interleukin 10 (IL-10) but only represent a minor population. Additionally, tumor-specific antibodies (Abs) also exhibit antitumor and protumor functions dependent on the Ab isotype. Transcription factor c-Maf has been suggested to contribute to the regulation of IL-10 in Breg, but the role of B cell c-Maf signaling in antitumor immunity and regulating Ab responses remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Conditional B cell c-Maf knockout (KO) and control mice were used to establish a KPC pancreatic cancer model and B16.F10 melanoma model. Tumor progression was evaluated. B cell and T cell phenotypes were determined by flow cytometry, mass cytometry, and cytokine\/chemokine profiling. Differentially expressed genes in B cells were examined by using RNA sequencing (RNA-seq). Peripheral blood samples were collected from healthy donors and patients with melanoma for B cell phenotyping.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with B cells from the spleen and lymph nodes (LN), B cells in the pancreas exhibited significantly less follicular phenotype and higher IL-10 production in na\u00efve mice. c-Maf deficiency resulted in a significant reduction of CD9\n                      <jats:sup>+<\/jats:sup>\n                      IL-10-producing Breg in the pancreas. Pancreatic ductal adenocarcinoma (PDAC) progression resulted in the accumulation of circulating B cells with the follicular phenotype and less IL-10 production in the pancreas. Notably, B cell c-Maf deficiency delayed PDAC tumor progression and resulted in proinflammatory B cells. Further, tumor volume reduction and increased effective T cells in the tumor-draining LN were observed in B cell c-Maf KO mice in the B16.F10 melanoma model. RNA-seq analysis of isolated B cells revealed that B cell c-Maf signaling modulates immunoglobulin-associated genes and tumor-specific Ab production. We furthermore demonstrated c-Maf-positive B cell subsets and an increase of IL-10-producing B cells after incubation with IL-4 and CD40L in the peripheral blood of patients with melanoma.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study highlights that B cell c-Maf signaling drives tumor progression through the modulation of Breg, inflammatory responses, and tumor-specific Ab responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2024-009861","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T04:21:51Z","timestamp":1732767711000},"page":"e009861","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["B cell c-Maf signaling promotes tumor progression in animal models of pancreatic cancer and melanoma"],"prefix":"10.1136","volume":"12","author":[{"given":"Qian","family":"Zhong","sequence":"first","affiliation":[{"name":"UofL Health Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Hao","sequence":"additional","affiliation":[{"name":"The Hiram C. Polk, Jr., MD Department of Surgery, University of Louisville, Louisville, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Li","sequence":"additional","affiliation":[{"name":"UofL Health Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongling","family":"Ning","sequence":"additional","affiliation":[{"name":"UofL Health Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"UofL Health Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Hu","sequence":"additional","affiliation":[{"name":"UofL Health Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M","family":"McMasters","sequence":"additional","affiliation":[{"name":"The Hiram C. 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