{"doi":"10.1136/jitc-2021-002603","title":"Type 17 immunity promotes the exhaustion of CD8<sup>+</sup> T cells in cancer","abstract":"Background Multiple types of immune cells producing IL-17 are found in the tumor microenvironment. However, their roles in tumor progression and exhaustion of CD8 + tumor-infiltrating lymphocytes (TILs) remain unclear. Methods To determine the role of type 17 immunity in tumor, we investigated the growth of B16F10 melanoma and the exhaustion of CD8 + TILs in Il17a −/− mice, Il17a Cre R26 DTA mice, RORγt inhibitor-treated mice, or their respective control mice. Adoptive transfer of tumor-specific IL-17-producing T cells was performed in B16F10-bearing congenic mice. Anti-CD4 or anti-Ly6G antibodies were used to deplete CD4 + T cells or CD11b + Gr-1 hi myeloid cells in vivo , respectively. Correlation between type 17 immunity and T cell exhaustion in human cancer was evaluated by interrogating TCGA dataset. Results Depletion of CD4 + T cells promotes the exhaustion of CD8 + T cells with a concomitant increase in IL-17-producing CD8 + T (Tc17) cells in the tumor. Unlike IFN-γ-producing CD8 + T (Tc1) cells, tumor-infiltrating Tc17 cells exhibit CD103 + KLRG1 − IL-7Rα hi tissue resident memory-like phenotypes and are poorly cytolytic. Adoptive transfer of IL-17-producing tumor-specific T cells increases, while depletion of IL-17-producing cells decreases, the frequency of PD-1 hi Tim3 + TOX + terminally exhausted CD8 + T cells in the tumor. Blockade of IL-17 or RORγt pathway inhibits exhaustion of CD8 + T cells and also delays tumor growth in vivo . Consistent with these results, human TCGA analyses reveal a strong positive correlation between type 17 and CD8 + T cell exhaustion signature gene sets in multiple cancers. Conclusion IL-17-producing cells promote terminal exhaustion of CD8 + T cells and tumor progression in vivo , which can be reversed by blockade of IL-17 or RORγt pathway. These findings unveil a novel role for IL-17-producing cells as tumor-promoting cells facilitating CD8 + T cell exhaustion, and propose type 17 immunity as a promising target for cancer immunotherapy.","journal":"Journal for ImmunoTherapy of Cancer","year":2021,"id":158109,"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":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":666392,"name":"Da‐Sol Kuen","orcid":"0000-0003-1184-5183","position":1,"is_corresponding":false},{"id":667211,"name":"Choong-Hyun Koh","orcid":null,"position":2,"is_corresponding":false},{"id":667212,"name":"Hyung-Don Kim","orcid":null,"position":3,"is_corresponding":false},{"id":666393,"name":"Seon Hee Chang","orcid":"0000-0002-9389-508X","position":4,"is_corresponding":false},{"id":666394,"name":"Sehui Kim","orcid":"0000-0002-6640-3051","position":5,"is_corresponding":false},{"id":666395,"name":"Yoon Kyung Jeon","orcid":"0000-0001-8466-9681","position":6,"is_corresponding":false},{"id":97052,"name":"Young‐Jun Park","orcid":"0000-0003-2901-6949","position":7,"is_corresponding":false},{"id":666396,"name":"Garam Choi","orcid":"0000-0003-1375-105X","position":8,"is_corresponding":false},{"id":666397,"name":"Jiyeon Kim","orcid":"0000-0003-0537-838X","position":9,"is_corresponding":false},{"id":364498,"name":"Keon Wook Kang","orcid":"0000-0003-2867-8940","position":10,"is_corresponding":false},{"id":666398,"name":"Hye Young Kim","orcid":"0000-0001-5978-512X","position":11,"is_corresponding":false},{"id":667213,"name":"Suk-Jo Kang","orcid":null,"position":12,"is_corresponding":false},{"id":666399,"name":"Shin Hwang","orcid":"0000-0002-9045-2531","position":13,"is_corresponding":false},{"id":666400,"name":"Eui‐Cheol Shin","orcid":"0000-0002-6308-9503","position":14,"is_corresponding":false},{"id":666401,"name":"Chang‐Yuil Kang","orcid":"0000-0002-1843-6967","position":15,"is_corresponding":false},{"id":278638,"name":"Chen Dong","orcid":"0000-0002-0084-9130","position":16,"is_corresponding":false},{"id":666402,"name":"Yeonseok Chung","orcid":"0000-0001-5780-4841","position":17,"is_corresponding":false},{"id":615160,"name":"Byung Seok Kim","orcid":"0000-0002-4318-4570","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-18T23:44:26.210708Z","pmid":"34083422","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":[]}