Genetic variation in immune genes creates inter-individual differences in immune traits. We are investigating the implications of these differences for cancer risk, progression and response to therapy. By jointly analyzing matched tumor and normal genomic data, we have found that individual immune genotypes can influence the evolution of tumor genomes, shape the tumor immune microenvironment and modify response to immunotherapy treatment. These studies will ultimately guide development of precision immunotherapies.
Abstract The anti-cancer immune response against mutated peptides of potential immunological relevance (neoantigens) is primarily attributed to MHC-I-restricted cytotoxic CD8+ T cell responses. MHC-II-restricted CD4+ T cells also drive anti-tumor responses, but their relation to neoantigen selection and tumor evolution has not been systematically studied.
Abstract MHC-I molecules expose the intracellular protein content on the cell surface, allowing T cells to detect foreign or mutated peptides. The combination of six MHC-I alleles each individual carries defines the sub-peptidome that can be effectively presented.