OS01.4.A A DETECTABLE ANTITUMOR IMMUNE RESPONSE IS PRESENT IN GLIOMAS, BUT IS PROFOUNDLY DAMPED BY CHEMOTHERAPY

Abstract BACKGROUND Until now, immunotherapy has been disappointing in gliomas. Promising results in cancer neoantigen (NeoAg)-directed vaccines have been seen, but final outcomes remain poor. We need a better comprehension of the factors associated with effectively immunogenic NeoAgs along with clinical features that correlate with detectable immune responses. MATERIAL AND METHODS We prospectively enrolled glioma patients from our institution in the IDeATIon project (NCT03706625) exploring tumors occurring in immunosuppressed conditions or in immune-privileged sites such as the CNS. We performed whole exome and RNA sequencing of tumor samples along with patients HLA typing. Using state of the art algorithms and personalized filters, we predicted cancer NeoAg sequences and expression. Peripheral blood mononuclear cells (PBMC) were collected in a subset of patients, and their reactivity to NeoAg-derived peptides was assessed ex vivo using ELISpot assays to validate in silico-predicted immunogenicity. RESULTS We enrolled 36 prospective glioma patients (IDH mutant, n=10; IDH wildtype, n=26). To test the ability of our pipeline to identify the most immunologically relevant NeoAgs among others, we privileged the inclusion of mismatch-repair (MMR)-deficient (MMRd) gliomas (n=21, of which 12 post-temozolomide and 9 de novo), given their expected high NeoAg burden. The median number of predicted immunogenic NeoAgs from 21 patients with both WES and RNASeq data was 274 and was higher for MMRd gliomas (1540 vs. 58, p