Exosomes derived from colorectal cancer cells suppress B-cell mediated anti-tumor immunity.

Exosomes derived from cancer cells significantly influence the tumor immune microenvironment and can limit the efficacy of immunotherapy. However, the impact of exosomes on B cell-dependent anti-tumor immunity remains poorly understood. Here, we demonstrate that exosomes secreted by MC38 (MC38-Exos), a murine colorectal cancer cell line, induce B cells to adopt immunosuppressive phenotypes. MC38-Exos inhibits B cell proliferation and survival. Additionally, MC38-Exos induce B cells to acquire characteristics of regulatory B cells, including the upregulation of IL-10 and TGF-β. Finally, B cells treated with MC38-Exos impair the functional efficacy of CD8 T cells. Transcriptome analysis reveals that MC38-Exos markedly suppresses gene pathways associated with B cell receptor (BCR) signaling, as well as antigen processing and presentation in B cells, but up-regulates genes involving apoptosis pathway. Mechanistically, NF-κB pathway was enriched in KEGG analysis, and was validated by western blot. Finally, inhibition of MC38-Exo in vivo activates B-cell mediated anti-tumor immunity. Thus, MC38-Exo has a profound effect of transcriptome of B cells and attenuates B cell-dependent anti-tumor immunity, supporting the rationale for targeted exosome therapy in human colorectal cancer.