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

Description: 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).

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Last updated: 2022-06-03