Abstract PR04: Temporal single cell profiling identifies B-cell specific checkpoint molecules that regulate anti-tumor immunity

Abstract

Abstract B cells play key roles in both innate and adaptive immunity. Distinct specialized B cell subsets engage a range of responses from antigen presentation to antibody production and B cells are one of the most abundant cell types of tumor infiltrating leukocytes (TILs), especially in melanoma. However, their role in anti-tumor immunity remains unclear. Here, we examined the B cell repertoire at single cell resolution from tumor-infiltrating B cells and tumor-draining lymph nodes (dLN) and identify and characterize a subset of B cells expressing the checkpoint molecule TIM-1 and a unique transcriptional signature, including multiple co-inhibitory molecules such as PD-1, TIM-3, TIGIT and LAG-3. While conditional deletion of these co-inhibitory molecules on B cells had little or no effect on tumor burden, selective deletion of Havcr1 (the gene encoding TIM-1) in B cells both dramatically inhibited tumor growth and enhanced effector T cell responses. Mechanistically, loss of TIM-1 enhanced the type 1 interferon response in B cells, which augmented B cell activation and increased antigen presentation and co-stimulation, resulting in increased expansion of tumor-specific effector T cells. Our results demonstrate that manipulation of TIM-1-expressing B cells enables engagement of the second arm of adaptive immunity to promote anti-tumor immunity and inhibit tumor growth. Citation Format: Lloyd Bod. Temporal single cell profiling identifies B-cell specific checkpoint molecules that regulate anti-tumor immunity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr PR04.