{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:04:26Z","timestamp":1789643066906,"version":"4.0.0"},"reference-count":49,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"unspecified","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA012197"],"award-info":[{"award-number":["P30CA012197"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA272724"],"award-info":[{"award-number":["R01CA272724"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["F31AI194729"],"award-info":[{"award-number":["F31AI194729"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32 AI007401"],"award-info":[{"award-number":["T32 AI007401"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,8,29]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Altered O-glycosylation is a hallmark of many adenocarcinomas and is often characterized by expression of the Tn antigen. However, the role of B cells in protection against Tn-expressing solid tumors remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We generated a colorectal tumor cell line (CMT93) lacking\n                      <jats:italic>Cosmc<\/jats:italic>\n                      , resulting in high Tn expression. Using mice with defined B-cell abnormalities, including deficiencies in B cells, IgM secretion, natural IgM, and B-cell receptor (BCR) repertoire diversity, we investigated the contribution of B cells and secreted antibody to immunity against Tn-expressing colorectal tumors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Cosmc<\/jats:italic>\n                      -deficient tumors grew more rapidly than parental tumors, and IgM deposition was observed within tumors from wild-type mice, suggesting a potential role for antibody in antitumor defense. Tumor-reactive serum IgM, including Tn-reactive IgM, was present in na\u00efve mice. B cell-deficient muMT, V\n                      <jats:sub>H<\/jats:sub>\n                      B\n                      <jats:sub>1-8<\/jats:sub>\n                      transgenic mice with a restricted BCR repertoire, CD19\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice deficient in natural IgM, and \u03bcS\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice unable to secrete IgM, lacked tumor-reactive IgM and showed increased tumor burdens, suggesting a protective role for secreted tumor-reactive IgM. Lack of tumor-reactive IgM in V\n                      <jats:sub>H<\/jats:sub>\n                      B\n                      <jats:sub>1-8<\/jats:sub>\n                      transgenic and \u03bcS\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice was associated with significant alterations in tumor-infiltrating leukocyte composition. Relative to wild-type mice, tumors from V\n                      <jats:sub>H<\/jats:sub>\n                      B\n                      <jats:sub>1-8<\/jats:sub>\n                      transgenic and \u03bcS\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice exhibited significantly increased PD-L1\n                      <jats:sup>hi<\/jats:sup>\n                      Ly6G\n                      <jats:sup>+<\/jats:sup>\n                      Ly6C\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD11b\n                      <jats:sup>+<\/jats:sup>\n                      myeloid cells, but reduced B, T, and natural killer cells, along with reduced major histocompatibility complex class II expression on tumor-associated dendritic cells. Moreover, tumor draining lymph nodes from V\n                      <jats:sub>H<\/jats:sub>\n                      B\n                      <jats:sub>1-8<\/jats:sub>\n                      transgenic and \u03bcS\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice showed significant reductions in antibody-secreting cells, including IgG\n                      <jats:sup>+<\/jats:sup>\n                      plasmablasts, which corresponded with decreased IgM and IgG deposition on tumors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings support a role for B cells and secreted IgM in restraining the growth of Tn-expressing solid tumors and shaping antitumor immunity against tumors with aberrant O-glycosylation.<\/jats:p>\n                  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