IMMU-16. SOMATIC MUTATIONS IN HUMAN LEUKOCYTE ANTIGEN GENES AND ANTIGEN PRESENTATION PATHWAY GENES IN MALIGNANT GLIOMA

Abstract Immunotherapeutic approaches in cancer aim to booster T cell mediated immune responses. Tumor-specific cells recognize target via human leukocyte antigen (HLA) molecules before specific lysis is initiated. Malignant gliomas are known for their immunoevasive and immunosuppressive properties which impede effective tumor-specific responses, including clinical responses checkpoint inhibition. Our was investigate whether somatic mutation HLA genes presentation pathway present malignant gliomas. METHODS We performed next generation sequencing 138 patients, matched tumor blood samples from 100 IDHwt glioblastomas, 25 IDHmut astrocytomas 13 oligodendrogliomas. Sequencing on peripheral class I (HLA-A, -B, -C), II (HLA-DR, -DP, -DQ), non-classical (HLA-E, -F, -G, -H), MICA/B, TAP1/2 beta2 microglobulin (B2M). Identified calls were validated using targeted nanopore sequencing. RESULTS In total, we identified 28 mutations based Illumina Mutations located HLA-B (2 mutations), HLA-C (1), B2M (2), HLA-DQA1 (4), HLA-DQB1 HLA-DPB1 HLA-E HLA-F HLA-G (3), HLA-H MICA MICB TAP1 (1) TAP2 (1). No found HLA-A HLA-DRB1. A frequency cutoff of 5% applied. Additional (n = 46) below this identified. The 30 patients (21.7%). Some harbored up 7-8 multiple presenting genes. Most the (MHC polypeptide–related sequence A) gene locus, engaged by NKG2D ligand broadly expressed NK cells, gd ab cells. CONCLUSION study demonstrates that frequently