IgM promotes antitumor immunity to a Tn-expressing solid tumor.

Authors

Hope L Nzuki, Jamie E Jennings-Gee, Michaela Trivette, Timothy H Mosher, Alexis E Adams-Sims, Abigail A Hegarty, Karen M Haas

Published in

Journal for immunotherapy of cancer. Volume 14. Issue 9. Sep 17, 2026. Epub Sep 17, 2026.

Abstract

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.
We generated a colorectal tumor cell line (CMT93) lacking Cosmc, 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.
Cosmc-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 naïve mice. B cell-deficient muMT, V_HB_1-8 transgenic mice with a restricted BCR repertoire, CD19^-/- mice deficient in natural IgM, and μS^-/- 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_HB_1-8 transgenic and μS^-/- mice was associated with significant alterations in tumor-infiltrating leukocyte composition. Relative to wild-type mice, tumors from V_HB_1-8 transgenic and μS^-/- mice exhibited significantly increased PD-L1^hiLy6G⁺Ly6C^-CD11b⁺ 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_HB_1-8 transgenic and μS^-/- mice showed significant reductions in antibody-secreting cells, including IgG⁺ plasmablasts, which corresponded with decreased IgM and IgG deposition on tumors.
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.

PMID:
42754287
Bibliographic data and abstract were imported from PubMed on 18 Sep 2026.

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