J Clin Invest. 2022 Mar 15;132(6). doi: 10.1172/JCI157665.
Tumor-infiltrating B cells exert antitumor effects by producing antibodies against tumor-associated antigens. Conversely, B cells may promote tumors through the production of factors that dampen antitumor immunity. In this issue of the JCI, Bing Yang, Zhen Zhang, et al. investigated the roles of B cell receptor (BCR) signaling in antitumor immunity, focusing on the role of an Asia-specific variant of human immunoglobulin G1 (IgG1) containing a Gly396 to Arg396 substitution (hIgG1-G396R) in colorectal cancer (CRC). Epidemiological analysis revealed an association between hIgG1-G396R and progression-free survival in CRC. Human samples and mouse models of CRC showed plasma cells, as opposed to B cells, infiltrating the tumor microenvironment. Notably, patients with the hIgG1-G396R variant had increased CD8+ T cells, dendritic cells, and tertiary lymphoid structure density. These findings indicate that the hIgG1-G396R variant represses tumorigenesis by enhancing B cell responses, and suggest that modulating BCR signaling could improve the efficacy of immunotherapy in cancer.
肿瘤浸润 B 细胞通过产生针对肿瘤相关抗原的抗体发挥抗肿瘤作用。相反，B 细胞可能通过产生抑制抗肿瘤免疫的因子来促进肿瘤。在本期《临床研究杂志》中，Bing Yang、Zhen Zhang 等人研究了 B 细胞受体 (BCR) 信号在抗肿瘤免疫中的作用，重点研究了含有甘氨酸 396 突变为精氨酸 396 取代的人免疫球蛋白 G1 (hIgG1-G396R) 在结直肠癌 (CRC) 中的作用。流行病学分析显示 hIgG1-G396R 与 CRC 的无进展生存期相关。CRC 的人类样本和小鼠模型显示浆细胞而不是 B 细胞浸润肿瘤微环境。值得注意的是，具有 hIgG1-G396R 变异的患者具有增加的 CD8+T 细胞、树突状细胞和三级淋巴结构密度。这些发现表明，hIgG1-G396R 变异通过增强 B 细胞反应抑制肿瘤发生，并提示调节 BCR 信号可能提高癌症免疫治疗的疗效。
