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

Sanja Stevanović, Anna Pasetto, Sarah R. Helman, Jared J. Gartner, Todd D. Prickett, Bryan Howie, Harlan S. Robins, Paul F. Robbins, Christopher A. Klebanoff, Steven A. Rosenberg, Christian S. Hinrichs

Research output: Contribution to journalArticle

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 Tcell therapy. Remarkably, immunodominant Tcell reactivities were directed againstmutated neoantigens or a cancer germline antigen, rather than canonical viral antigens.Tcells targeting viral tumor antigens did not display preferential in vivo expansion. Both viral and nonviral tumor antigen-specificTcells resided predominantly in the programmed cell death 1 (PD-1)-expressing Tcell compartment, which suggests that PD-1 blockade may unleash diverse antitumor Tcell reactivities.These findings suggest a new paradigm of targeting nonviral antigens in immunotherapy of virally associated cancers.

Original languageEnglish (US)
Pages (from-to)200-205
Number of pages6
JournalScience
Volume356
Issue number6334
DOIs
StatePublished - Apr 14 2017
Externally publishedYes

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Neoplasm Antigens
Immunotherapy
Viral Tumor Antigens
Neoplasms
Cell Death
Antigens
Viral Antigens
Uterine Cervical Neoplasms
T-Lymphocytes
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Stevanović, S., Pasetto, A., Helman, S. R., Gartner, J. J., Prickett, T. D., Howie, B., ... Hinrichs, C. S. (2017). Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. Science, 356(6334), 200-205. https://doi.org/10.1126/science.aak9510

Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. / Stevanović, Sanja; Pasetto, Anna; Helman, Sarah R.; Gartner, Jared J.; Prickett, Todd D.; Howie, Bryan; Robins, Harlan S.; Robbins, Paul F.; Klebanoff, Christopher A.; Rosenberg, Steven A.; Hinrichs, Christian S.

In: Science, Vol. 356, No. 6334, 14.04.2017, p. 200-205.

Research output: Contribution to journalArticle

Stevanović, S, Pasetto, A, Helman, SR, Gartner, JJ, Prickett, TD, Howie, B, Robins, HS, Robbins, PF, Klebanoff, CA, Rosenberg, SA & Hinrichs, CS 2017, 'Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer', Science, vol. 356, no. 6334, pp. 200-205. https://doi.org/10.1126/science.aak9510
Stevanović S, Pasetto A, Helman SR, Gartner JJ, Prickett TD, Howie B et al. Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. Science. 2017 Apr 14;356(6334):200-205. https://doi.org/10.1126/science.aak9510
Stevanović, Sanja ; Pasetto, Anna ; Helman, Sarah R. ; Gartner, Jared J. ; Prickett, Todd D. ; Howie, Bryan ; Robins, Harlan S. ; Robbins, Paul F. ; Klebanoff, Christopher A. ; Rosenberg, Steven A. ; Hinrichs, Christian S. / Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. In: Science. 2017 ; Vol. 356, No. 6334. pp. 200-205.
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