IMMU-28. THE INTRA-TUMORAL SPATIAL HETEROGENEITY OF T CELL ANTIGENS IN GLIOBLASTOMA: AN INTEGRATED MULTI-OMICS APPROACH

Abstract This study investigates the intratumoral heterogeneity of T cell antigen presentation in 15 newly diagnosed glioblastoma patients. Our multi-omics approach includes mass spectrometry-based immunopeptidome analysis, next-generation sequencing (whole-exome and RNA sequencing), imaging cytometry performed on biopsies deriving from necrotic core (NEC), gadolinium contrast-enhancing region (T1), peritumoral infiltrating zone (INF, 5-ALA positive). A total 24493 unique HLA class I 17394 II peptides were identified. Comparative profiling our a benign tissue database (in-house; n = 429 donors combined with ligand atlas (https://hla-ligand-atlas.org)) revealed that 20% ligands are exclusive. Of these ligands, 21%, 15% exclusively presented INF, T1, or NEC zone, respectively. Here, we focused INF-specific antigens as this is likely to remain after tumor resection gives rise recurrence. Interestingly, two showed frequency 45% patient cohort. One originated BAALC (Brain acute leukemia cytoplasmic protein) one NCAN (Neurocan protein), which both known be glioblastoma-associated proteins. Immunogenicity pre-selected candidate was assessed autologous expanded cells set novel promising targets for immunotherapy. Integrated RNA/DNA also enabled identification neoepitopes tumor- region-specific mutations. Furthermore, contributed investigating immune compartment microenvironment high dimensionality spatial resolution. In conclusion, characterized intra-tumoral regional antigens. landscape can used informed design immunotherapy strategies against glioblastoma.