CTLA‐4 inhibition facilitates follicular T and B cell interaction and the production of tumor‐specific antibodies

Abstract

AbstractImmune checkpoint inhibitors (ICIs) induce activation and expansion of cytotoxic T cells. To depict a comprehensive immune cell landscape reshaped by the CTLA‐4 checkpoint inhibitor, we performed single‐cell RNA sequencing in a mouse syngeneic tumor transplant model. After CTLA‐4 inhibition, tumor regression was accompanied by massive immune cell expansion, especially in T and B cells. We found that B cells in tumor transplant represented follicular, germinal center and plasma B cells, some of which shared identical B cell receptor clonotypes and possessed tumor reactivity. Furthermore, the posttreatment tumor contained a tertiary lymphoid‐like structure with intermingled T and B cells. These data suggest germinal center formation within the tumor mass and in situ differentiation of tumor‐specific plasma cells. Taken together, our data provide a panoramic view of the immune microenvironment after CTLA‐4 inhibition and suggest a role for tumor‐specific B cells in antitumor immunity.