{"doi":"10.1084/jem.20210693","title":"IL-17–induced HIF1α drives resistance to anti–PD-L1 via fibroblast-mediated immune exclusion","abstract":"Increasing evidence suggests that intratumoral inflammation has an outsized influence on antitumor immunity. Here, we report that IL-17, a proinflammatory cytokine widely associated with poor prognosis in solid tumors, drives the therapeutic failure of anti-PD-L1. By timing the deletion of IL-17 signaling specifically in cancer-associated fibroblasts (CAFs) in late-stage tumors, we show that IL-17 signaling drives immune exclusion by activating a collagen deposition program in murine models of cutaneous squamous cell carcinoma (cSCC). Ablation of IL-17 signaling in CAFs increased the infiltration of cytotoxic T cells into the tumor mass and sensitized otherwise resistant cSCC to anti-PD-L1 treatment. Mechanistically, the collagen deposition program in CAFs was driven by IL-17-induced translation of HIF1α, which was mediated by direct binding of Act1, the adaptor protein of IL-17 receptor, to a stem-loop structure in the 3' untranslated region (UTR) in Hif1α mRNA. Disruption of Act1's binding to Hif1α mRNA abolished IL-17-induced collagen deposition and enhanced anti-PD-L1-mediated tumor regression.","journal":"The Journal of Experimental Medicine","year":2022,"id":239242,"datarank":0.5897738449086489,"base_score":3.9318256327243257,"endowment":3.9318256327243257,"self_citation_contribution":0.5897738449086489,"citation_network_contribution":0.0,"self_endowment_contribution":0.5897738449086489,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":50,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":240320,"name":"Junjie Zhao","orcid":"0000-0002-0105-0531","position":1,"is_corresponding":false},{"id":864408,"name":"Tomasz Herjan","orcid":"0000-0003-2504-8572","position":2,"is_corresponding":false},{"id":486342,"name":"Lingzi Hong","orcid":"0000-0002-9485-6445","position":3,"is_corresponding":false},{"id":240319,"name":"Yun Liao","orcid":"0000-0002-0829-8986","position":4,"is_corresponding":false},{"id":292271,"name":"Caini Liu","orcid":"0000-0002-9314-7145","position":5,"is_corresponding":false},{"id":196520,"name":"Kommireddy Vasu","orcid":"0000-0002-7608-7566","position":6,"is_corresponding":false},{"id":256160,"name":"Han Wang","orcid":"0000-0002-1442-4539","position":7,"is_corresponding":false},{"id":864583,"name":"Austin Thompson","orcid":"0000-0002-1097-033X","position":8,"is_corresponding":false},{"id":196523,"name":"Paul L Fox","orcid":"0000-0002-6033-1528","position":9,"is_corresponding":false},{"id":864584,"name":"Brian Gastman","orcid":"0000-0003-2691-3409","position":10,"is_corresponding":false},{"id":227640,"name":"Xiao Li","orcid":"0000-0003-2566-0796","position":11,"is_corresponding":false},{"id":240331,"name":"Xiaoxia Li","orcid":"0000-0002-4872-9525","position":12,"is_corresponding":false},{"id":27363,"name":"Xing Chen","orcid":"0000-0001-9727-3598","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:22:36.865157Z","pmid":"35389431","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":[]}