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

• DOI: 10.1016/j.celrep.2023.112508
• Publication Date: 2023-05-11T15:46:02Z
• Authors: Sayuri Miyauchi; Sangwoo S. Kim; Riley N. Jones; Lin Zhang; Kripa Guram; Sonia Sharma; Stephen P. Schoen...; Ezra E.W. Cohen; Joseph A. Califano; Andrew B. Sharabi
• Keywords: Sting; Cancer Immunotherapy

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