{"doi":"10.1073/pnas.2221707120","title":"Steroid receptor coactivator 3 is a key modulator of regulatory T cell–mediated tumor evasion","abstract":"Steroid receptor coactivator 3 (SRC-3) is most strongly expressed in regulatory T cells (Tregs) and B cells, suggesting that it plays an important role in the regulation of Treg function. Using an aggressive E0771 mouse breast cell line syngeneic immune-intact murine model, we observed that breast tumors were \"permanently eradicated\" in a genetically engineered tamoxifen-inducible Treg-cell-specific SRC-3 knockout (KO) female mouse that does not possess a systemic autoimmune pathological phenotype. A similar eradication of tumor was noted in a syngeneic model of prostate cancer. A subsequent injection of additional E0771 cancer cells into these mice showed continued resistance to tumor development without the need for tamoxifen induction to produce additional SRC-3 KO Tregs. SRC-3 KO Tregs were highly proliferative and preferentially infiltrated into breast tumors by activating the chemokine (C-C motif) ligand (Ccl) 19/Ccl21/chemokine (C-C motif) receptor (Ccr)7 signaling axis, generating antitumor immunity by enhancing the interferon-γ/C-X-C motif chemokine ligand (Cxcl) 9 signaling axis to facilitate the entrance and function of effector T cells and natural killer cells. SRC-3 KO Tregs also show a dominant effect by blocking the immune suppressive function of WT Tregs. Importantly, a single adoptive transfer of SRC-3 KO Tregs into wild-type E0771 tumor-bearing mice can completely abolish preestablished breast tumors by generating potent antitumor immunity with a durable effect that prevents tumor reoccurrence. Therefore, treatment with SRC-3-deleted Tregs represents an approach to completely block tumor growth and recurrence without the autoimmune side effects that typically accompany immune checkpoint modulators.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":331741,"datarank":0.49983067652628066,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.0,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"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":511946,"name":"Prashi Jain","orcid":"0000-0003-3746-7758","position":1,"is_corresponding":false},{"id":1057144,"name":"Yosef Gilad","orcid":"0009-0006-8475-9197","position":2,"is_corresponding":false},{"id":32290,"name":"Yan Xia","orcid":"0000-0003-4509-0137","position":3,"is_corresponding":false},{"id":483826,"name":"Nuri Sung","orcid":null,"position":4,"is_corresponding":false},{"id":1057145,"name":"Mi Jin Park","orcid":"0000-0002-7748-3886","position":5,"is_corresponding":false},{"id":723983,"name":"Adam Dean","orcid":null,"position":6,"is_corresponding":false},{"id":380968,"name":"Rainer B. Lanz","orcid":"0000-0003-1713-8527","position":7,"is_corresponding":false},{"id":460773,"name":"Jianming Xu","orcid":"0000-0002-8208-9162","position":8,"is_corresponding":false},{"id":304055,"name":"Clifford C. Dacso","orcid":"0000-0002-0710-1678","position":9,"is_corresponding":false},{"id":317011,"name":"David M. Lonard","orcid":"0000-0002-4876-8479","position":10,"is_corresponding":false},{"id":304057,"name":"Bert W. O’Malley","orcid":"0000-0003-3332-1399","position":11,"is_corresponding":false},{"id":482744,"name":"Sang Jun Han","orcid":"0000-0003-3692-6756","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:09:25.015646Z","pmid":"37253006","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":[]}