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Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer.


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.

SUBMITTER: Stevanovic S 

PROVIDER: S-EPMC6295311 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer.

Stevanović Sanja S   Pasetto Anna A   Helman Sarah R SR   Gartner Jared J JJ   Prickett Todd D TD   Howie Bryan B   Robins Harlan S HS   Robbins Paul F PF   Klebanoff Christopher A CA   Rosenberg Steven A SA   Hinrichs Christian S CS  

Science (New York, N.Y.) 20170401 6334


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 c  ...[more]

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