Identification of MHC-I regulators in HPV+ HNC cells and HPV oncoprotein-expressing keratinocytes.

Accordingly, MHC-I antigen presentation is frequently dysregulated in cancer, including human papillomavirus-positive head and neck cancer (HPV+ HNC), as a strategy for immune evasion. Downregulation of MHC-I is thought to be a major obstacle in HPV+ HNC treatment, particularly for non-responders to immunotherapies.

We recently found that membrane-associated RING-CH finger 8 (MARCHF8) induced by the HPV oncoproteins ubiquitinates MHC-I. However, the mechanism of how ubiquitinated MHC-I is degraded in HPV+ HNC remains to be elucidated. To identify key regulators of MHC-I expression, we performed genome-wide CRISPR/Cas9 knockout screens in two HPV+ HNC cell lines (SCC90 and SCC152) and normal keratinocytes expressing the HPV oncoprotein E6 and E7 (N/Tert-1 E6E7).