{"doi":"10.1126/scitranslmed.adp2124","title":"Heterogeneous cellular responses to hyperthermia support combined intraperitoneal hyperthermic immunotherapy for ovarian cancer mouse models","abstract":"<jats:p>\n            The benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer remains controversial, hindering the development of rational combination therapies based on hyperthermia (HT). This study reports the preliminary results of the neoadjuvant HIPEC (NHIPEC) trial (ChiCTR2000038173), demonstrating enhanced tumor response in high-grade serous ovarian cancer with NHIPEC. Through single-cell RNA sequencing analysis, we identified both homogeneous and heterogeneous cellular responses to HT within the tumor and microenvironment. Epithelial-mesenchymal transition–activated tumor cells and matrix metallopeptidase 11 (MMP-11)\n            <jats:sup>+</jats:sup>\n            cancer-associated fibroblasts (CAFs) exhibited greater reductions and higher sensitivity to HT. CUT&amp;Tag and RNA sequencing integration unveiled the differential binding programs and transcriptional regulatory mechanisms of HSF1 under normothermia (NT) and HT in tumor cells and CAFs. Furthermore, HT ameliorated the immunosuppressive tumor microenvironment, and in vivo mouse models confirmed the combined antitumor effects of HT and programmed cell death ligand 1 blockade. These findings provide an innovative strategy for rational combination therapy with HT in ovarian cancer.\n          </jats:p>","journal":"Science Translational Medicine","year":2025,"id":619749,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1599549,"name":"Xiaoyan Kang","orcid":"0009-0005-7779-7681","position":1,"is_corresponding":false},{"id":1207387,"name":"Faming Zhao","orcid":"0000-0002-8238-3863","position":2,"is_corresponding":false},{"id":1599550,"name":"Yaoyuan Cui","orcid":"0000-0003-2145-2455","position":3,"is_corresponding":false},{"id":649440,"name":"Yu Fu","orcid":"0000-0002-5952-2300","position":4,"is_corresponding":false},{"id":72358,"name":"Xiaohang Yang","orcid":"0000-0001-5192-5706","position":5,"is_corresponding":false},{"id":513218,"name":"Jingjing Yin","orcid":"0000-0003-4843-613X","position":6,"is_corresponding":false},{"id":1433851,"name":"Wenting Li","orcid":"0000-0001-8220-4696","position":7,"is_corresponding":false},{"id":1599551,"name":"Junpeng Fan","orcid":"0000-0002-9413-408X","position":8,"is_corresponding":false},{"id":649438,"name":"Bin Yang","orcid":"0000-0002-6218-2773","position":9,"is_corresponding":false},{"id":1599552,"name":"Zixuan Fang","orcid":"0009-0005-2251-2343","position":10,"is_corresponding":false},{"id":649447,"name":"Tianyu Qin","orcid":"0000-0002-5897-871X","position":11,"is_corresponding":false},{"id":1599553,"name":"Xucui Zhuang","orcid":"0000-0003-3082-0707","position":12,"is_corresponding":false},{"id":299699,"name":"Yiting Liu","orcid":"0000-0001-9368-3290","position":13,"is_corresponding":false},{"id":1599554,"name":"Chenzhao Feng","orcid":null,"position":14,"is_corresponding":false},{"id":1599556,"name":"Yunyi Yang","orcid":"0009-0007-3574-0913","position":15,"is_corresponding":false},{"id":649436,"name":"Funian Lu","orcid":"0000-0003-4864-4967","position":16,"is_corresponding":false},{"id":440096,"name":"Li Zhang","orcid":"0000-0003-0006-4066","position":17,"is_corresponding":false},{"id":1183533,"name":"Weihao Chen","orcid":"0000-0003-2993-0183","position":18,"is_corresponding":false},{"id":1599560,"name":"Miaofang Wu","orcid":null,"position":19,"is_corresponding":false},{"id":1550298,"name":"Ning Du","orcid":null,"position":20,"is_corresponding":false},{"id":25247,"name":"Xia Sheng","orcid":"0000-0002-8742-7343","position":21,"is_corresponding":false},{"id":280981,"name":"Xin Zhou","orcid":"0000-0003-4015-4787","position":22,"is_corresponding":false},{"id":1346179,"name":"Jing Li","orcid":"0000-0003-3209-8973","position":23,"is_corresponding":false},{"id":542838,"name":"Gang Chen","orcid":"0000-0002-8320-6594","position":24,"is_corresponding":false},{"id":649449,"name":"Chaoyang Sun","orcid":"0000-0003-2469-1638","position":25,"is_corresponding":false},{"id":1599548,"name":"Xingyuan Hu","orcid":"0000-0001-5225-377X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Heterogeneous cellular responses to hyperthermia support combined intraperitoneal hyperthermic immunotherapy for ovarian cancer mouse models","abstract":"<jats:p>\n            The benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer remains controversial, hindering the development of rational combination therapies based on hyperthermia (HT). This study reports the preliminary results of the neoadjuvant HIPEC (NHIPEC) trial (ChiCTR2000038173), demonstrating enhanced tumor response in high-grade serous ovarian cancer with NHIPEC. Through single-cell RNA sequencing analysis, we identified both homogeneous and heterogeneous cellular responses to HT within the tumor and microenvironment. Epithelial-mesenchymal transition–activated tumor cells and matrix metallopeptidase 11 (MMP-11)\n            <jats:sup>+</jats:sup>\n            cancer-associated fibroblasts (CAFs) exhibited greater reductions and higher sensitivity to HT. CUT&amp;Tag and RNA sequencing integration unveiled the differential binding programs and transcriptional regulatory mechanisms of HSF1 under normothermia (NT) and HT in tumor cells and CAFs. Furthermore, HT ameliorated the immunosuppressive tumor microenvironment, and in vivo mouse models confirmed the combined antitumor effects of HT and programmed cell death ligand 1 blockade. These findings provide an innovative strategy for rational combination therapy with HT in ovarian cancer.\n          </jats:p>","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40073154","pmcid":null,"openalex_id":"https://openalex.org/W4408345629","authors":[],"funders":[],"total_grants":0,"fwci":7.2896,"citation_percentile":0.97237418,"influential_citations":0,"citation_trend":[{"year":2025,"count":3},{"year":2026,"count":5}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.science.org/doi/pdf/10.1126/scitranslmed.adp2124","host_type":"publisher"},{"url":"https://doi.org/10.1126/scitranslmed.adp2124","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40073154","host_type":"repository"}],"fields_of_study":["Ovarian cancer diagnosis and treatment","Cancer Cells and Metastasis","Extracellular vesicles in disease"],"mesh_terms":["Cancer-Associated Fibroblasts","Hyperthermic Intraperitoneal Chemotherapy","Animals","Combined Modality Therapy","Disease Models, Animal","Female","Humans","Hyperthermia, Induced","Immunotherapy","Ovarian Neoplasms","Gene Expression Regulation, Neoplastic","Cell Line, Tumor","Mice","Epithelial-Mesenchymal Transition","Single-Cell Analysis","Tumor Microenvironment"],"keywords":["Ovarian cancer","Cancer research","Tumor microenvironment","Hyperthermic intraperitoneal chemotherapy","In vivo","Medicine","Hyperthermia","Immunotherapy","Cancer","Cancer cell","Biology","Internal medicine","Tumor cells","Cytoreductive surgery"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T08:20:29.527224Z","pmid":null,"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":[]}