Abstract The primary objective of the Immunogenomics Core is to perform comprehensive immunophenotyping, functional analyses, and genetic and epigenetic monitoring in peripheral blood and the tumor microenvironment and investigate tumor antigen-specific immune responses for the immunotherapeutic approaches being developed and tested in Individual Research Projects 1-3 of the Roswell Park Ovarian Cancer SPORE. It will be also responsible for immunologic and genomic assays for Career Enhancement Program (CEP) and Developmental Research Program (DRP). In conjunction with the Biospecimen and Pathology Core, morphology and localization of immune cells on pre- and post-immunotherapy tumor sections will be analyzed by highly multiplexed Imaging Mass Cytometry (IMC). Additionally, in conjunction with the Biostatistics and Bioinformatics Core, neoantigens, transcriptome analysis, epigenetic changes and TCR sequencing will be determined for Individual Research Project 1 and 3. The Core will routinely provide SPORE investigators high quality, state-of- the-art CyTOF, IMC, Seahorse assays, cell culture, cell isolation, flow cytometry, ELISPOT, ELISA, multiplex cytokine bead array, RNA-seq, whole exome sequencing, TCR-seq, and Methyl-Seq. The specific aims of the Immunogenomics Core are to: 1) Design and optimize immunologic and genomic assays for Individual Research Projects, CEP and DRP, and provide state-of-the-art immunophenotyping, transcriptome analysis, TCR sequencing, epigenetic changes and functional analyses of immune cells in peripheral blood and tumor microenvironment of patients who receive advanced immunotherapies in the Ovarian Cancer SPORE. 2) Run whole exome sequencing for tumor and peripheral blood samples to identify mutations and HLA types and confirm T-cell reactivity against the predicted neoantigens for DC-peptide vaccine in Individual Research Project 3. In addition to these established immunoassays, the Immunogenomics Core will be developing new methodologies/markers and making them available to the SPORE investigators. It also has a significant educational role, working with all SPORE investigators, including PIs, technicians and young investigators on their assay development, proper use of instrumentation, and interpretation of their data.