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Science. 2017 Apr 14;356(6334):200-205. doi: 10.1126/science.aak9510.

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

Author information

1
Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. sanjastevanovic@hotmail.com hinrichs@mail.nih.gov.
2
Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA.
3
Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
4
Adaptive Biotechnologies, Seattle, WA 98102, USA.
5
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
6
Center for Cell Engineering and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
7
Parker Institute for Cancer Immunotherapy, New York, NY 10065, USA.

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.

PMID:
28408606
DOI:
10.1126/science.aak9510
[Indexed for MEDLINE]

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