TMIC-06. IMMUNE MICROENVIRONMENT IN CYSTIC GBM

Abstract

The study objective was to characterize the immune microenvironment in cystic glioblastoma (GBM). We retrospectively reviewed the records of 298 consecutive newly diagnosed and recurrent adult GBM patients treated at our hospital from Jan 2011 to Jun 2017. 23 (7.7%) had cystic tumors and 17 had cystic tumor components. We were able to analyze 23 of these cystic GBM (cGBM) cases. We observed that overall survival in cGBM group is longer than in noncystic counterparts. In 17 samples, 16 were PTEN+, and all of these had TILS CD3, CD4, CD8 within the tumor and in surrounding vessels, 7/17 cGBM were PDL-1+ (>1%). T cells (CD8+, CD4+, and CD8+CD4+), B cells and NK cells were detected in the cystic fluid of cGBM cases. T memory cells (CD4+CD25-CD127+) but not Treg cells were also detected in the cystic fluid. The proportion of active T cells (CD69+) in the cystic fluid was higher than in control PBMC. Immunosuppressive cells Treg and MDSC populations were lower in the cystic fluid than in PBMC. The ProcartaPlex Human Cytokine Panel (34 plex) and IPA data analysis a variety of chemokines were detected in the GBM cyst fluid. IL-6, GRO-alpha, IL-8, IP-10, MCP-1, TNF-a, IL-4, IL-27 were higher in the peripheral blood serum cGBM patients versus non-cystic GBM patients; however, the inhibitory cytokine IL-10 is lower in cyst fluid or PB serum. These results suggest that the mechanism of cystic formation in cGBM could be due to activation of the host immune system. Higher levels of chemokines in the cystic fluid of cGBM patients could enhance recruitment of lymphocytes into the tumor. Intact PTEN status as observed in 16/17 cGBM patients in our study, is critical for anti-glioma immune function and may have played a role in improved survival in our study.