UC Davis

Tumor infiltrating B lymphocytes (TIL-Bs), that include B cells and plasma cells are increasingly recognized as favorable prognostic markers in multiple cancer types. The precise mechanisms underlying TIL-B associated anti-tumor immunity is an active area of investigation. Here, we identified CD79A transcript levels as a reliable quantifier of B lymphocytes. Using this marker in the cancer genome atlas (TCGA) and Gene tissue expression (GTEx) to assess transcriptomic data for 16 distinct tumors and normal tissues respectively, from a total of nearly 10,000 patients, we demonstrate that significant tumor B cell infiltration correlated with survival for some but not all tumor types. CD79A is a stronger predictor of overall survival (OS) in Non-small cell lung cancer (NSCLC) than CD8A transcripts. Further, leveraging published single cell RNA sequencing (scRNA-seq) data from NSCLC, we identified the presence and enrichment of unique CD11c expressing TIL-Bs in tumor tissue from treatment-naïve NSCLC patients, compared to normal adjacent tissue and peripheral blood. In the tumor environment these CD11c+ TIL-Bs, when compared to CD11c- B cells, were found to be preferentially localized near CD4+ T cells. Antigen recall with/without T cell help, mimicked in vitro by stimulation of freshly isolated TIL-Bs with anti-IgG with/without CD40 agonist resulted in a strong expansion of CD11c+ B cells and their rapid differentiation into plasmablasts and their precursors. Furthermore, the BCR-mediated expansion of CD11c+ TIL-Bs was associated with secretion of effector cytokines, including IL-12, IL-21, and TNF-a, that are known to enhance anti-tumor immunity. Taken together, we demonstrate that this novel population of CD11c+ TIL-B’s can actively respond to antigen and/or CD4 T cell help, identifying a potentially new cell subset to harness in anti-cancer therapeutic approaches and/or a potential novel prognostic biomarker for cancer outcome prognosis.