Pre-treatment Molecular Characterizations of Tumors from Patients Who Receive Immune Checkpoint Therapies

Immune checkpoint inhibitors yield clinical benefit in many cancer types, but molecular predictors of response have not yet been robustly characterized. In this study, we pursued whole exome sequencing (WES) of pre-treatment tumors from patients treated with immune checkpoint therapies - including monoclonal antibodies targeting programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4). Using these data, we aim to apply computational pipelines for mutation-calling, neoantigen prediction, and other analyses to validate pre-existing hypotheses regarding response to immune checkpoint therapies and discover new relationships with greater power. Further, by pursuing genomic characterization of tumors from patients with a variety of cancer types, we hope to describe molecular features of intrinsically sensitive or resistant tumors that are both context-specific and shared across cancer types.]]> Primary tumor tissue samples from patients who received anti-PD-1/PD-L1 or anti-CTLA-4 therapy alone or in combination with other immunotherapies, targeted therapies, or cytotoxic chemotherapies were obtained for whole exome sequencing and whole transcriptome sequencing. DNA was extracted from formalin-fixed paraffin-embedded primary tissue as well as from whole blood for use as a normal DNA comparison. All patients were also required to have matched normal tissue available from fresh whole blood or archival normal tissue.]]>