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

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

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Carcinoma, Squamous Cell / therapy*
  • Carcinoma, Squamous Cell / virology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Female
  • Human papillomavirus 16 / immunology
  • Human papillomavirus 18 / immunology
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / transplantation
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology*
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / therapy*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation
  • Uterine Cervical Neoplasms / therapy*
  • Uterine Cervical Neoplasms / virology

Substances

  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 16
  • E7 protein, Human papillomavirus type 18
  • Oncogene Proteins, Viral
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Repressor Proteins