Abstract
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.
Highlights
Tumor-infiltrating B cells exert antitumor effects by producing antibodies against tumor-associated antigens
Antibodies in turn can impact downstream immune responses, including antibody-dependent cellular cytotoxicity (ADCC) by NK cells, phagocytosis by macrophages (ADCP), and antigen presentation and T cell priming by dendritic cells (DCs) [1, 2]
In ovalbumin-immunized mice expressing mIgG2c-G400R, wild-type mIgG2c, or mIgG2c with a truncated cytoplasmic tail, in which the B cell receptor (BCR) signals are sequentially reduced, the authors showed that the variant promoted differentiation of antigen-specific plasma cells and memory B cells
Summary
Tumor-infiltrating B cells exert antitumor effects by producing antibodies against tumor-associated antigens. Tumor-infiltrating B cells exert both antitumor and protumor effects, depending on their immunestimulatory or immune-suppressive activities, which vary with cancer type [1, 2]. To investigate the roles of BCR signaling modulation in antitumor immunity, the study in this issue of the JCI by Bing Yang, Zhen Zhang, et al [14] followed up on their recent report on an Asia-specific variant of human immunoglobulin G1 (IgG1) containing a Gly396 to Arg396 substitution (hIgG1-G396R) in colorectal cancer (CRC).
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