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.
Copyright © 2017, American Association for the Advancement of Science.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology*
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Carcinoma, Squamous Cell / therapy*
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Carcinoma, Squamous Cell / virology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology*
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Female
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Human papillomavirus 16 / immunology
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Human papillomavirus 18 / immunology
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Humans
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Immunotherapy, Adoptive / methods*
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Lymphocytes, Tumor-Infiltrating / immunology
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Lymphocytes, Tumor-Infiltrating / transplantation
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Oncogene Proteins, Viral / genetics
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Oncogene Proteins, Viral / immunology*
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Papillomavirus Infections / complications
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Papillomavirus Infections / therapy*
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Programmed Cell Death 1 Receptor / antagonists & inhibitors
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Programmed Cell Death 1 Receptor / genetics
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Programmed Cell Death 1 Receptor / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / immunology*
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T-Lymphocytes / immunology
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T-Lymphocytes / transplantation
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Uterine Cervical Neoplasms / therapy*
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Uterine Cervical Neoplasms / virology
Substances
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Antigens, Neoplasm
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DNA-Binding Proteins
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E6 protein, Human papillomavirus type 16
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E7 protein, Human papillomavirus type 18
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Oncogene Proteins, Viral
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PDCD1 protein, human
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Programmed Cell Death 1 Receptor
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Repressor Proteins