Characterization of neoantigen-specific T cells in cancer resistant to immune checkpoint therapies
Shamin Li, Yannick Simoni, Summer Zhuang, Austin M. Gabel, Shaokang Ma, Jonathan Chee, Laura Islas, Anthony Cessna, Jenette Creaney, Robert K. Bradley, Alec Redwood, Bruce Robinson, Evan W. Newell
Abstract
Significance Strongly implicated in effective antitumor immune responses, tumor mutation–derived antigens, or neoantigens, are one of the main targets for cancer vaccines despite uncertainty of the efficacy of this approach. Using a high-throughput screening method, we identify an endogenously immunogenic neoantigen in a commonly used mouse lung tumor model. We also found that the endogenous CD8 T cells specific for this neoantigen expand greatly upon treatment with immune checkpoint inhibitors or vaccination despite the lack of associated tumor regression in this model. In addition to informing neoantigen vaccination strategies and providing an accessible system for testing alternative therapeutics, our results provide insights into the mechanisms for the lack of response observed for a majority of patients treated with checkpoint blockade immunotherapies.