IMMU-11. IDENTIFICATION OF GLIOMA-ASSOCIATED REGULATORY B CELLS AND EFFECTS OF RITUXIMAB IMMUNOTHERAPY

Abstract

In the context of glioblastoma multiforme (GBM), immunotherapy remains a promising approach. However, the potent immunosuppression induced by GBM is one of the primary obstacles to finding effective immunotherapies. This immunosuppression is associated with high levels of immunosuppressive cytokines and a significant accumulation of both regulatory T cells (CD4+CD25+FoxP3+, Tregs) and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment. Other actors of the immune system may also play a role in glioma immunobiology, such as B cells, known to infiltrate gliomas. From a total of 60 GBM samples, we observed that 40% of GBM samples scored positive for CD20+B-cell infiltration, presenting a discrete perivascular distribution. The current fundamental work aims to elucidate the phenotype and function of gliomainfiltrating B cells in two different glioma experimental model, GL261 and CT2A. Our results showed that glioma-associated B cells are a unique activated B-cell subset that produces immunoregulatory cytokines IL-10, TGFb and IL35; and inhibitory ligands PD-L1 and the polivirus receptor CD155. Glioma-associated Bregs are activated by MDSC and interact with activated CD8 T cells and strongly suppress their expansion and cytotoxic function, suggestive of their pro-tumorigenic function. In accordance, B-cell depletion therapy (anti-CD20; Rituximab) improved significantly animal survival. This work highlights the potential involvement of B cells in glioblastoma physiopathology and provides crucial information about the mechanisms by which gliomas is able to modulate B-cell immunity.