IMMU-69. PROGNOSTIC IMPLICATION OF B-CELL INFILTRATE IN PATIENTS WITH GLIOBLASTOMA (GBM). (5th November 2018) - Mauldin, Ileana
Abstract: BACKGROUND: One of the purported reasons of ineffectiveness of immunotherapy for GBM is the meager immune response in the tumor microenvironment. We have observed that GBM can harbor dense B-cell infiltrate, but their prevalence and function is unknown. Pre-clinical studies have shown that B-cells can act as antigen-presenting cells which can stimulate T-cell proliferation; however, B-cells can also downregulate effector T-cells by secreting immunosuppressive cytokines including IL-10. Our study aims to determine the roles of B-cells in GBM and their association with patient outcomes. METHODS: Multiplexed immunohistochemistry, imaging and quantitation was performed on primary GBM samples obtained between 1/2008-8/2015. Intratumoral CD20 + B-cells and CD8 + T-cells infiltrate were enumerated from 3 serial GBM sections. Relevant prognostic clinical and molecular variables were reviewed. We also analyzed the association of MS4A1 gene encoding B-cell antigen CD20 with survival from the TCGA. RESULTS: We observed an average infiltrate of 5.5 CD20 + cells/mm 2 and 36.7 CD8 + cells/mm 2 tumor. B-cells were stratified into CD20 low (12 patients) and CD20 high groups (36 patients) with 0.24 B-cells/mm 2 cut off. Kaplan-Meier analyses indicated that the CD20 low group had better overall survival (OS) than the CD20 high cohort (31.7 versus 18.7 months; p=0.02), while a trend toward improved survival was observed with high CD8 + T-cell infiltration (p=0.06). Cox proportional hazard demonstrated an association between decreased OS and CD20 high cohort (HR=2.8, p=0.03), but no significance seen between CD8 + infiltration and OS (p=0.16). A positive correlation was detected between CD8 + and CD20 + density (p CONCLUSIONS: Our results suggest that B-cell infiltrate carries an inverse correlation with survival. We hypothesize that CD20 + B-cells may be regulatory B-cells, limiting immune activation in GBM. Further studies are underway to understand the role of B-cells in the GBM microenvironment.