{"doi":"10.3390/cancers15194905","title":"Stress Keratin 17 Is a Predictive Biomarker Inversely Associated with Response to Immune Check-Point Blockade in Head and Neck Squamous Cell Carcinomas and Beyond","abstract":"Low response rates in immune check-point blockade (ICB)-treated head and neck squamous cell carcinoma (HNSCC) drive a critical need for robust, clinically validated predictive biomarkers. Our group previously showed that stress keratin 17 (CK17) suppresses macrophage-mediated CXCL9/CXCL10 chemokine signaling involved in attracting activated CD8+ T cells into tumors, correlating with decreased response rate to pembrolizumab-based therapy in a pilot cohort of ICB-treated HNSCC (n = 26). Here, we performed an expanded analysis of the predictive value of CK17 in ICB-treated HNSCC according to the REMARK criteria and investigated the gene expression profiles associated with high CK17 expression. Pretreatment samples from pembrolizumab-treated HNSCC patients were stained via immunohistochemistry using a CK17 monoclonal antibody (n = 48) and subjected to spatial transcriptomic profiling (n = 8). Our findings were validated in an independent retrospective cohort (n = 22). CK17 RNA expression in pembrolizumab-treated patients with various cancer types was investigated for predictive significance. Of the 48 patients (60% male, median age of 61.5 years), 21 (44%) were CK17 high, and 27 (56%) were CK17 low. A total of 17 patients (35%, 77% CK17 low) had disease control, while 31 patients (65%, 45% CK17 low) had progressive disease. High CK17 expression was associated with a lack of disease control (p = 0.037), shorter time to treatment failure (p = 0.025), and progression-free survival (PFS, p = 0.004), but not overall survival (OS, p = 0.06). A high CK17 expression was associated with lack of disease control in an independent validation cohort (p = 0.011). PD-L1 expression did not correlate with CK17 expression or clinical outcome. CK17 RNA expression was predictive of PFS and OS in 552 pembrolizumab-treated cancer patients. Our findings indicate that high CK17 expression may predict resistance to ICB in HNSCC patients and beyond.","journal":"Cancers","year":2023,"id":371727,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9616,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1131746,"name":"Israa Laklouk","orcid":"0000-0001-9688-3167","position":1,"is_corresponding":false},{"id":783697,"name":"Athena E. Golfinos","orcid":"0000-0002-8365-1743","position":2,"is_corresponding":false},{"id":885516,"name":"Niki Gavrielatou","orcid":"0000-0003-1380-6831","position":3,"is_corresponding":false},{"id":782799,"name":"Jin Xu","orcid":"0000-0002-0869-0507","position":4,"is_corresponding":false},{"id":796844,"name":"Christopher Flynn","orcid":null,"position":5,"is_corresponding":false},{"id":635261,"name":"Aysenur Keske","orcid":"0000-0002-8975-4233","position":6,"is_corresponding":false},{"id":437916,"name":"Menggang Yu","orcid":"0000-0002-7904-3155","position":7,"is_corresponding":false},{"id":353966,"name":"Justine Y. Bruce","orcid":"0000-0002-5902-7430","position":8,"is_corresponding":false},{"id":774869,"name":"Wei Wang","orcid":"0000-0002-3422-0402","position":9,"is_corresponding":false},{"id":1131747,"name":"Cvetka Grašič Kuhar","orcid":"0000-0001-5047-4034","position":10,"is_corresponding":false},{"id":474844,"name":"Howard H. Bailey","orcid":"0000-0002-9149-3378","position":11,"is_corresponding":false},{"id":259501,"name":"Paul M. Harari","orcid":"0000-0002-6207-5505","position":12,"is_corresponding":false},{"id":271171,"name":"Huy Q. Dinh","orcid":"0000-0002-3307-1126","position":13,"is_corresponding":false},{"id":109014,"name":"David L. Rimm","orcid":"0000-0001-5820-4397","position":14,"is_corresponding":false},{"id":353965,"name":"Rong Hu","orcid":"0000-0002-1502-9848","position":15,"is_corresponding":false},{"id":328282,"name":"Paul F. Lambert","orcid":"0000-0001-7983-2755","position":16,"is_corresponding":false},{"id":412253,"name":"Megan B. Fitzpatrick","orcid":"0000-0001-7040-8018","position":17,"is_corresponding":false},{"id":881964,"name":"Taja Ložar","orcid":"0000-0003-2893-5580","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T01:15:49.453761Z","pmid":"37835599","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}