B细胞主导的炎症级联反应使ICI介导的结肠炎持续存在

Immune checkpoint inhibitor (ICI) therapy is often accompanied by inflammatory toxicities including ICI-colitis. Therapeutic options are limited because the mechanisms that predict its onset are unclear. We uncover a role for B cells in triggering the intestinal inflammatory cascade following ICIs. An increase in circulating B cells, particularly those with gut-homing markers, antigen-presenting capacity, and proinflammatory cytokine production, are found in both asymptomatic patients and mice which are susceptible to ICI-colitis. Furthermore, lack of B cells at the asymptomatic stage abrogates ICI-colitis by reducing the number of pathogenic intestinal T cells in mice. We find that latent microbial dysbiosis may underlie the B cell dysfunction in the asymptomatic stage that predisposes mice to the development of colitis following ICI therapy. Thus, our study examines the immunologic evolution underlying ICI-colitis and proposes B cell dysregulation as a critical initiating factor in this process and a potential biomarker for toxicity risk.