Year: 2026
Type: article
Abstract: Background 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. Methods 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. Results 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 H B 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 H B 1-8 transgenic and μS −/− mice was associated with significant alterations in tumor-infiltrating leukocyte composition. Relative to wild-type mice, tumors from V H B 1-8 transgenic and μS −/− mice exhibited significantly increased PD-L1 hi Ly6G + 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 H B 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. Conclusions 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.
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7213455201