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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
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Published on: February 28, 2019

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CXCL14 suppresses human papillomavirus-associated head and neck cancer through antigen-specific CD8+ T-cell responses

Joseph A Westrich1,2, Daniel W Vermeer3, Alexa Silva1

  • 1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.

Oncogene
|August 17, 2019
PubMed

Insights

Restoring CXCL14 chemokine expression in human papillomavirus (HPV)-positive head and neck cancer (HNC) suppresses tumor growth. This occurs by enhancing CD8+ T cell responses and restoring MHC-I expression, crucial for antitumor immunity.

Area of Science:

  • Immunology
  • Oncology
  • Virology

Background:

  • Human papillomavirus (HPV) oncoprotein E7 downregulates CXCL14, a chemokine critical for immune response.
  • HPV-positive head and neck cancer (HNC) progression involves immune evasion.
  • Restoring CXCL14 in HPV-positive HNC suppresses tumor growth via immune mechanisms.

Purpose of the Study:

  • To define the mechanism of CXCL14-mediated tumor suppression in HPV-positive HNC.
  • To investigate the roles of NK and T cells in CXCL14's antitumor effects.
  • To elucidate how CXCL14 influences the tumor microenvironment and immune cell interactions.

Main Methods:

  • Utilized a CD8+ T-cell receptor transgenic mouse model.
  • Assessed the requirement of CD8+ T cells for CXCL14-mediated tumor suppression.
  • Analyzed the impact of CXCL14 on Major Histocompatibility Complex class I (MHC-I) expression.
  • Investigated antigen specificity in CXCL14-mediated CD8+ T-cell responses.

Main Results:

  • CD8+ T cells are essential for CXCL14-mediated tumor suppression in HPV-positive HNC.
  • CXCL14 restores MHC-I expression on HPV-positive HNC cells, which is otherwise downregulated by HPV.
  • Tumor suppression is lost if MHC-I expression is knocked down, even with CXCL14 presence.
  • CXCL14-mediated antitumor CD8+ T-cell responses are antigen-specific.

Conclusions:

  • CXCL14 promotes antitumor immunity against HPV-positive HNC by restoring MHC-I expression on tumor cells.
  • CXCL14 enhances antigen-specific CD8+ T-cell responses, leading to tumor suppression.
  • Targeting CXCL14 could be a therapeutic strategy for HPV-positive HNC by reactivating anti-tumor immunity.

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