Genomic analysis to identify correlates of the inflamed tumor phenotype in patients with advanced malignancies receiving immunotherapy

This biomarker study will analyze tissues from patients with cancer who are receiving immunomodulatory treatment (or therapy that could be hypothesized to modulate the immune response), to correlate molecular/genetic features of the tumor cells, the host, and the intestinal microbiome with the immunologic phenotype of the tumor microenvironment. Recent data have suggested that patients with pre-existing T cell infiltration in the tumor microenvironment and/or an “inflamed” gene expression profile in tumor sites have better clinical outcome following treatment with several immunotherapeutic approaches. However, the mechanism by which this spontaneous anti-tumor immune response develops in only a subset of patients is not understood. Potential correlations between mutational patterns in the tumor, germline genetic polymorphisms, peripheral blood immune response parameters, and the composition of intestinal microbiota and the presence or absence of a T cell-infiltrated tumor microenvironment will be sought. Understanding these mechanisms will have important implications for future patient selection for treatment with immunotherapies and highlight new potential pathways for therapeutic development. Mechanisms of secondary resistance to immunotherapies also will be interrogated using tissues obtained at time of recurrence.