{"doi":"10.1084/jem.20232104","title":"Anti-PD-1 therapy triggers Tfh cell–dependent IL-4 release to boost CD8 T cell responses in tumor-draining lymph nodes","abstract":"Anti-PD-1 therapy targets intratumoral CD8+ T cells to promote clinical responses in cancer patients. Recent evidence suggests an additional activity in the periphery, but the underlying mechanism is unclear. Here, we show that anti-PD-1 mAb enhances CD8+ T cell responses in tumor-draining lymph nodes by stimulating cytokine production in follicular helper T cells (Tfh). In two different models, anti-PD-1 mAb increased the activation and proliferation of tumor-specific T cells in lymph nodes. Surprisingly, anti-PD-1 mAb did not primarily target CD8+ T cells but instead stimulated IL-4 production by Tfh cells, the major population bound by anti-PD-1 mAb. Blocking IL-4 or inhibiting the Tfh master transcription factor BCL6 abrogated anti-PD-1 mAb activity in lymph nodes while injection of IL-4 complexes was sufficient to recapitulate anti-PD-1 mAb activity. A similar mechanism was observed in a vaccine model. Finally, nivolumab also boosted human Tfh cells in humanized mice. We propose that Tfh cells and IL-4 play a key role in the peripheral activity of anti-PD-1 mAb.","journal":"The Journal of Experimental Medicine","year":2024,"id":419727,"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":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1209788,"name":"Marion V. Guérin","orcid":"0000-0003-2159-8518","position":1,"is_corresponding":false},{"id":1209789,"name":"Béatrice Corre","orcid":"0009-0001-2149-3583","position":2,"is_corresponding":false},{"id":1210422,"name":"Margot Bardou","orcid":null,"position":3,"is_corresponding":false},{"id":1209790,"name":"Ruby Alonso","orcid":"0000-0002-0884-967X","position":4,"is_corresponding":false},{"id":1209791,"name":"Erica Russo","orcid":"0000-0002-0997-1861","position":5,"is_corresponding":false},{"id":1209792,"name":"Zacarias Garcia","orcid":"0000-0003-0774-809X","position":6,"is_corresponding":false},{"id":1209793,"name":"L Feldmann","orcid":"0009-0002-3307-181X","position":7,"is_corresponding":false},{"id":1209794,"name":"Fabrice Lemaı̂tre","orcid":"0000-0003-2287-6129","position":8,"is_corresponding":false},{"id":1209795,"name":"Mathilde Dusséaux","orcid":"0000-0003-0131-3853","position":9,"is_corresponding":false},{"id":1209796,"name":"Capucine L. Grandjean","orcid":"0000-0002-2901-7186","position":10,"is_corresponding":false},{"id":1209797,"name":"Philippe Bousso","orcid":"0000-0002-6362-561X","position":11,"is_corresponding":false},{"id":1209787,"name":"Mathilde Ruggiu","orcid":"0009-0001-2739-5378","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T01:57:19.937291Z","pmid":"38417020","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":[]}