CXCL14 suppresses human papillomavirus-associated head and neck cancer through antigen-specific CD8+ T-cell responses by upregulating MHC-I expression

Joseph A. Westrich, Daniel W. Vermeer, Alexa Silva, Stephanie Bonney, Jennifer N. Berger, Louis Cicchini, Robert O. Greer, John I. Song, David Raben, Jill E. Slansky, John H. Lee, William C. Spanos, Dohun Pyeon

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Evasion of the host immune responses is critical for both persistent human papillomavirus (HPV) infection and associated cancer progression. We have previously shown that expression of the homeostatic chemokine CXCL14 is significantly downregulated by the HPV oncoprotein E7 during cancer progression. Restoration of CXCL14 expression in HPV-positive head and neck cancer (HNC) cells dramatically suppresses tumor growth and increases survival through an immune-dependent mechanism in mice. Although CXCL14 recruits natural killer (NK) and T cells to the tumor microenvironment, the mechanism by which CXCL14 mediates tumor suppression through NK and/or T cells remained undefined. Here we report that CD8+ T cells are required for CXCL14-mediated tumor suppression. Using a CD8+ T-cell receptor transgenic model, we show that the CXCL14-mediated antitumor CD8+ T-cell responses require antigen specificity. Interestingly, CXCL14 expression restores major histocompatibility complex class I (MHC-I) expression on HPV-positive HNC cells downregulated by HPV, and knockdown of MHC-I expression in HNC cells results in loss of tumor suppression even with CXCL14 expression. These results suggest that CXCL14 enacts antitumor immunity through restoration of MHC-I expression on tumor cells and promoting antigen-specific CD8+ T-cell responses to suppress HPV-positive HNC.

Original languageEnglish (US)
Pages (from-to)7166-7180
Number of pages15
JournalOncogene
Volume38
Issue number46
DOIs
StatePublished - Nov 14 2019
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Westrich, J. A., Vermeer, D. W., Silva, A., Bonney, S., Berger, J. N., Cicchini, L., Greer, R. O., Song, J. I., Raben, D., Slansky, J. E., Lee, J. H., Spanos, W. C., & Pyeon, D. (2019). CXCL14 suppresses human papillomavirus-associated head and neck cancer through antigen-specific CD8+ T-cell responses by upregulating MHC-I expression. Oncogene, 38(46), 7166-7180. https://doi.org/10.1038/s41388-019-0911-6