Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer
- Sanja Stevanović1,*,
- Anna Pasetto2,
- Sarah R. Helman1,
- Jared J. Gartner2,
- Todd D. Prickett2,
- Bryan Howie3,
- Harlan S. Robins3,4,
- Paul F. Robbins2,
- Christopher A. Klebanoff5,6,
- Steven A. Rosenberg2,
- Christian S. Hinrichs1,*
Abstract
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.