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

Immune 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 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 anti-tumor immunity. Overall design: BALB/c mice were inoculated subcutaneously with 2 × 105 CT26 cells. Mice were injected intraperitoneally with 100㎍ anti-CTLA-4(9H10) or phosphate-buffered solution (PBS) on days 5, 8, and 11 after tumor inoculation. Mice were sacrificed 13 days after tumor inoculation. Tissue specimens were analyzed by immunofluorescence tissue staining, scRNAseq(10x genemics).