{"doi":"10.1073/pnas.2404916121","title":"Peripheral-derived regulatory T cells contribute to tumor-mediated immune suppression in a nonredundant manner","abstract":"Identifying tumor-mediated mechanisms that impair immunity is instrumental for the design of new cancer therapies. Regulatory T cells (Tregs) are a key component of cancer-derived immune suppression; however, these lymphocytes are necessary to prevent systemic autoimmunity in mice and humans, and thus, direct targeting of Tregs is not a clinical option for cancer patients. We have previously demonstrated that excising transcription factor Kruppel-like factor 2 ( Klf2 ) within the T cell lineage blocks the generation of peripheral-derived Tregs (pTregs) without impairing production of thymic-derived Tregs. Using this mouse model, we have now demonstrated that eliminating pTregs is sufficient to delay/prevent tumor malignancy without causing autoimmunity. Cancer-bearing mice that expressed KLF2 converted tumor-specific CD4 + T cells into pTregs, which accumulated in secondary lymphoid organs and impaired further T cell effector activity. In contrast, pTreg-deficient mice retained cancer-specific immunity, including improved T cell infiltration into “cold” tumors, reduced T cell exhaustion in tumor beds, restricted generation of tumor-associated myeloid-derived suppressor cells, and the continued production of circulating effector T cells that arose in a cancer-dependent manner. Results indicate that tumor-specific pTregs are critical for early stages of cancer progression and blocking the generation of these inhibitory lymphocytes safely delays/prevents malignancy in preclinical models of melanoma and prostate cancer.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":443144,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"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":1257287,"name":"Paul T. King","orcid":"0000-0001-5197-1163","position":1,"is_corresponding":false},{"id":822298,"name":"Justin Hackett","orcid":"0000-0002-3377-1499","position":2,"is_corresponding":false},{"id":1257761,"name":"Hervé C. Gérard","orcid":null,"position":3,"is_corresponding":false},{"id":1257762,"name":"Rajmund Michal Niwinski","orcid":null,"position":4,"is_corresponding":false},{"id":1257288,"name":"Lan Wu","orcid":"0000-0001-6032-083X","position":5,"is_corresponding":false},{"id":302765,"name":"Luc Van Kaer","orcid":"0000-0001-5275-2309","position":6,"is_corresponding":false},{"id":264006,"name":"Gregory Dyson","orcid":"0000-0001-9783-8464","position":7,"is_corresponding":false},{"id":299803,"name":"Heather M. Gibson","orcid":"0000-0003-2652-8252","position":8,"is_corresponding":false},{"id":356145,"name":"Alexander D. Borowsky","orcid":"0000-0003-3117-9202","position":9,"is_corresponding":false},{"id":924325,"name":"Eric Sebzda","orcid":null,"position":10,"is_corresponding":false},{"id":923830,"name":"Md Moazzem Hossain","orcid":"0000-0002-8355-6690","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T02:01:24.471942Z","pmid":"39207730","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":[]}