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

• Sanja ^[3] ; Anna ^[1] ; Sarah R. ^[2]
  1. [1] Pasetto
  2. [2] Helman
  3. [3] Stevanović

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• Localización: Science, ISSN 0036-8075, Vol. 356, Nº 6334, 2017, págs. 200-205
• Idioma: inglés
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• Resumen

  • 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.