The Presence of CD11c+ B Cells with Potent Effector Memory Phenotype in Lung Adenocarcinoma Correlates with Overall Patient Survival

Tumor-infiltrating B lymphocytes (TIL-Bs) are increasingly recognized as favorable prognostic markers in multiple cancer types and the mechanisms underlying this are being actively investigated. In this study of TIL-Bs, we identified CD79A as a reliable quantifier of B lymphocytes and evaluated transcriptomic data for 15 distinct tumors using 8,720 samples of treatment naïve patients from The Cancer Genome Atlas and normal tissues from Gene Tissue Expression. B-lymphocyte infiltration correlated with survival for some but not all tumors. In lung adenocarcinoma (LUAD), CD79A levels were strongly predictive of overall survival, while CD8A transcripts were not, indicating that leukocytic infiltration per se does not explain the B-cell's impact. Single-cell RNA sequencing and flow cytometry identified increased relative numbers of CD11c+ B cells in treatment-naïve LUAD patients compared to normal tissue and blood. In LUAD, CD11c+ TIL-Bs were localized near CD4+ T cells and in vitro stimulation with anti-IgG with/without CD40 agonist resulted in expansion and rapid differentiation. Stimulation also induced IL-12, IL-21, and TNF-α secretion, which are cytokines known to enhance antitumor immunity. Overall, the data indicte that CD11c+ TIL-Bs are a potential target for anticancer therapeutic approaches and/or a potential prognostic biomarker for cancer prognosis.