Li Yunqiao, Bhargava Raag, Tran Jenny Tuyet, Blane Tanya R, Peng Linghang, Luan Fangkun, Huang Zhe, Zhang Zefan, Sun Yunfan, Xiao Changchun, Nemazee David
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
Nat Commun. 2025 May 14;16(1):4454. doi: 10.1038/s41467-025-59622-4.
B cells engage in anti-tumor immunity but how they contribute to cancer suppression remains unclear. We report that inhibiting plasma cell differentiation either in IgMi mice lacking Igh elements needed for antibody secretion or in mice with B cell-specific knockout of Blimp-1 (Blimp-1 BcKO) promotes rather than inhibits antitumor immunity and increases numbers of activated B cells. Deficiency of Blimp-1 in tumor-infiltrating B cells generates a unique transcription profile associated with expansion of mutated clones targeting cognate tumor cells. Major histocompatibility complex class II (MHC II) is required for anti-tumor efficacy. Blimp-1-deficient B cells have increased expression of CD80 and CD86 costimulatory molecules that enhance effector T cell function. The Blimp-1 inhibitor valproic acid suppresses tumor growth in a B cell-dependent manner. Thus, inhibition of plasma cell differentiation results in enhanced tumor-specific antigen presentation by B cells and thereby tumor repression, suggesting a potential avenue of immunotherapy against cancer.
B细胞参与抗肿瘤免疫，但它们如何促进癌症抑制仍不清楚。我们报告称，在缺乏抗体分泌所需Igh元件的IgMi小鼠中或在B细胞特异性敲除Blimp-1的小鼠（Blimp-1 BcKO）中抑制浆细胞分化会促进而非抑制抗肿瘤免疫，并增加活化B细胞的数量。肿瘤浸润性B细胞中Blimp-1的缺乏产生了一种独特的转录谱，与靶向同源肿瘤细胞的突变克隆的扩增相关。主要组织相容性复合体II类（MHC II）是抗肿瘤疗效所必需的。缺乏Blimp-1的B细胞中协同刺激分子CD80和CD86的表达增加，这增强了效应T细胞的功能。Blimp-1抑制剂丙戊酸以B细胞依赖的方式抑制肿瘤生长。因此，抑制浆细胞分化会导致B细胞增强肿瘤特异性抗原呈递，从而抑制肿瘤，这提示了一种潜在的癌症免疫治疗途径。
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