Heterogeneous cellular responses to hyperthermia support combined intraperitoneal hyperthermic immunotherapy for ovarian cancer mouse models
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)<sup>+</sup> cancer-associated fibroblasts (CAFs) exhibited greater reductions and higher sensitivity to HT. CUT&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.
Authors
- Xia Sheng (ORCID: https://orcid.org/0000-0002-8742-7343)
- Ning Du (ORCID: https://orcid.org/0000-0001-5394-8776)
- Faming Zhao (ORCID: https://orcid.org/0000-0002-8238-3863)
- Yunyi Yang (ORCID: https://orcid.org/0009-0007-3574-0913)
- Tianyu Qin (ORCID: https://orcid.org/0000-0002-5897-871X)
- X. S. Kang
- Yu Fu (ORCID: https://orcid.org/0000-0002-5952-2300)
- Bin Yang (ORCID: https://orcid.org/0000-0002-6218-2773)
- Chenzhao Feng (ORCID: https://orcid.org/0000-0001-6018-7768)
- Xingyuan Hu (ORCID: https://orcid.org/0000-0001-5225-377X)
- Jingjing Yin (ORCID: https://orcid.org/0000-0003-2325-2713)
- Zixuan Fang
- Xucui Zhuang (ORCID: https://orcid.org/0000-0003-3082-0707)
- Xiaohang Yang (ORCID: https://orcid.org/0000-0002-6760-5157)
- Yaoyuan Cui
- Chaoyang Sun (ORCID: https://orcid.org/0000-0003-2469-1638)
- Jing Li (ORCID: https://orcid.org/0000-0002-9609-5846)
- Gang Chen (ORCID: https://orcid.org/0000-0002-8320-6594)
- Yiting Liu (ORCID: https://orcid.org/0000-0001-9368-3290)
- Weihao Chen (ORCID: https://orcid.org/0000-0002-6709-9223)
- Xin Zhou (ORCID: https://orcid.org/0000-0001-5973-7304)
- Funian Lu (ORCID: https://orcid.org/0000-0003-4864-4967)
- Miao‐fang Wu
- Li Zhang (ORCID: https://orcid.org/0000-0002-8502-4946)
- W M Li (ORCID: https://orcid.org/0000-0002-1257-4410)
- Junpeng Fan (ORCID: https://orcid.org/0000-0002-9413-408X)
Institutions
- Sun Yat-sen University (CN)
- Hainan University (CN)
- Sun Yat-sen Memorial Hospital (CN)
- First Affiliated Hospital of Shihezi University Medical College (CN)
- Tongji Hospital (CN)
- Qilu Hospital of Shandong University (CN)
- Huazhong University of Science and Technology (CN)
- China Medical University (CN)
Publication Details
- Journal
- Science Translational Medicine
- Published
- 2025-03-12
- DOI
- https://doi.org/10.1126/scitranslmed.adp2124
- Citations
- 6
- Primary Topic
- Ovarian cancer diagnosis and treatment
- Type
- article
- Field-Weighted Citation Impact
- 10.19