{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE324nnn/GSE324388/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324388"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Identification of MHC-I regulators in HPV+ HNC cells and HPV oncoprotein-expressing keratinocytes.","description":"Recognition of tumor antigens presented by major histocompatibility complex class I (MHC-I) on cancer cells is critical for the antitumor T cell response. 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). Among the top pathways enriched in the negative regulators were genes involved in the autophagy pathway, a catabolic process that recycles cellular components. Futher studies demonstrated that inhibition of autophagy, specifically autophagy initiation, restored surface MHC-I expression in HPV+ HNC cells. Taken together, these studies have identified a mechanism of immune evasion in HPV+ HNC through identifying genes involved in MHC-I protein degradation by autophagy.","dates":{"publication":"2026/09/17"},"accession":"GSE324388","cross_references":{"GSM":["GSM9574788","GSM9574789","GSM9574790","GSM9574791","GSM9574792","GSM9574793"],"GPL":["18573"],"GSE":["324388"],"taxon":["Homo sapiens"]}}