Altered phenotypes of tumor-infiltrating B cells in response to exhausted CD8+ T cells

Abstract

Abstract During chronic infections, such as cancer, tumor antigen presentation and inflammation mobilizes a heterogeneous T cell response, consisting of cells in unique states of differentiation and functional capacity. We assayed tumor-infiltrating lymphocytes from human breast, colorectal and melanoma tumors. By flow cytometry, we observed T cells undergoing exhaustion as characterized by a loss of effector functions (IFNy, TNFa, and IL-2) and expressing surface markers PD-1, TIM-3 and CD39. Although this cell intrinsic signature of T cell exhaustion has been well studied, its association with B lymphocytes is still obscure. CXCL13 expression was one of the most significantly upregulated genes in tumor exhausted T cells, as observed by single-cell sequencing. We identified infiltration of CD138+ CD38− plasma cells and CD138−CD38−CD19+ B cells in human breast, colorectal and melanoma tumors. In addition, we observed, by immunohistochemistry, large tertiary lymphoid structures (TLS) in human breast cancer tumors composed of CD20+ B cells and T cells in close proximity. Finally, we evaluated the differential expression of immune modulatory molecules GARP, CD39 and CD73 on B cell subsets from tumors. Further work will investigate the inhibitory or stimulatory role of B cells on tumor-infiltrating T cells.