IMMU-69. PROGNOSTIC IMPLICATION OF B-CELL INFILTRATE IN PATIENTS WITH GLIOBLASTOMA (GBM)

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.

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.

We observed an average infiltrate of 5.5 CD20⁺ cells/mm²and 36.7 CD8⁺cells/mm²tumor. B-cells were stratified into CD20^low(12 patients) and CD20^highgroups (36 patients) with 0.24 B-cells/mm² cut off. Kaplan-Meier analyses indicated that the CD20^lowgroup had better overall survival (OS) than the CD20^highcohort (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^highcohort (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

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.