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April 13, 2017

[Report] Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer

ScienceNOW - Fetched: April 13th, 2017, 3:00pm UTC
Immunotherapy has clinical activity in certain virally associated cancers. However, the tumor antigens targeted in successful treatments remain poorly defined. We used a personalized immunogenomic approach to elucidate the global landscape of antitumor T cell responses in complete regression of human papillomavirus–associated metastatic cervical cancer after tumor-infiltrating adoptive T cell therapy. Remarkably, immunodominant T cell reactivities were directed against mutated neoantigens or a cancer germline antigen, rather than canonical viral antigens. T cells targeting viral tumor antigens did not display preferential in vivo expansion. Both viral and nonviral tumor antigen–specific T cells resided predominantly in the programmed cell death 1 (PD-1)–expressing T cell compartment, which suggests that PD-1 blockade may unleash diverse antitumor T cell reactivities. These findings suggest a new paradigm of targeting nonviral antigens in immunotherapy of virally associated cancers. Authors: Sanja Stevanović, Anna Pasetto, Sarah R. Helman, Jared J. Gartner, Todd D. Prickett, Bryan Howie, Harlan S. Robins, Paul F. Robbins, Christopher A. Klebanoff, Steven A. Rosenberg, Christian S. Hinrichs

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