Human papillomavirus E5 suppresses immunity via inhibition of the immunoproteasome and STING pathway

Sayuri Miyauchi; Sangwoo S. Kim; Riley N. Jones; Lin Zhang; Kripa Guram; Sonia Sharma; Stephen P. Schoenberger; Ezra E.W. Cohen; Joseph A. Califano; Andrew B. Sharabi

Cell Reports (May 2023)

Human papillomavirus E5 suppresses immunity via inhibition of the immunoproteasome and STING pathway

Sayuri Miyauchi,
Sangwoo S. Kim,
Riley N. Jones,
Lin Zhang,
Kripa Guram,
Sonia Sharma,
Stephen P. Schoenberger,
Ezra E.W. Cohen,
Joseph A. Califano,
Andrew B. Sharabi

Affiliations

Sayuri Miyauchi: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, CA 92037, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA
Sangwoo S. Kim: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, CA 92037, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA
Riley N. Jones: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, CA 92037, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA
Lin Zhang: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, CA 92037, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA
Kripa Guram: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, CA 92037, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA
Sonia Sharma: La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Stephen P. Schoenberger: La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Ezra E.W. Cohen: Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA
Joseph A. Califano: Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA; Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, La Jolla, CA 92037, USA
Andrew B. Sharabi: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, CA 92037, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 5
p. 112508

Abstract

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Summary: The role that human papillomavirus (HPV) oncogenes play in suppressing responses to immunotherapy in cancer deserves further investigation. In particular, the effects of HPV E5 remain poorly understood relative to E6 and E7. Here, we demonstrate that HPV E5 is a negative regulator of anti-viral interferon (IFN) response pathways, antigen processing, and antigen presentation. Using head and neck cancer as a model, we identify that E5 decreases expression and function of the immunoproteasome and that the immunoproteasome, but not the constitutive proteasome, is associated with improved overall survival in patients. Moreover, immunopeptidome analysis reveals that HPV E5 restricts the repertoire of antigens presented on the cell surface, likely contributing to immune escape. Mechanistically, we discover a direct interaction between E5 and stimulator of interferon genes (STING), which suppresses downstream IFN signaling. Taken together, these findings identify a powerful molecular mechanism by which HPV E5 limits immune detection and mediates resistance to immunotherapy.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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