title: Cryo-thermal therapy elicits potent anti-tumor immunity by inducing extracellular Hsp70-dependent MDSC differentiation.
abstract: Achieving control of metastatic disease is a long-sought goal in cancer therapy. Treatments that encourage a patient's own immune system are bringing new hopes in reaching such a goal. In clinic, local hyperthermia and cryoablation have been explored to induce anti-tumor immune responses against tumors. We have also developed a novel therapeutic modality of cryo-thermal treatment by alternating liquid nitrogen (LN2) cooling and radio frequency (RF) heating, and better therapeutic effect was achieved in treating metastatic cancer in animal model. In this study, we investigated the mechanism of systemic immune response elicited by cryo-thermal therapy. In the 4T1 murine mammary carcinoma model, we found that local cryo-thermal therapy resulted in a considerable reduction of distant lung metastases, and improved long-term survival. Moreover, results of tumor re-challenge experiments indicated generation of a strong tumor-specific immune memory after the local treatment of primary tumors. Our further study indicated that cryo-thermal therapy caused an elevated extracellular release of Hsp70. Subsequently, Hsp70 induced differentiation of MDSCs into mature DCs, contributing to the relief of MDSCs-mediated immunosuppression and ultimately the activation of strong anti-tumor immune response. Our findings reveal new insight into the mechanism of robust therapeutic effects of cryo-thermal therapy against metastatic cancers.
authors.affiliation: The School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.|Neurosurgery Department, Ruijin Hospital,School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: The School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Aili
authors.initials: A
authors.lastname: Zhang
authors.affiliation: The School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.affiliation: The School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: The School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Lisa X
authors.initials: LX
authors.lastname: Xu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D017679:Cryotherapy / Q000379:methods*; D003713:Dendritic Cells / Q000166:cytology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006979:Hyperthermia, Induced / Q000379:methods*; D008175:Lung Neoplasms / Q000556:secondary* / Q000628:therapy*; D008325:Mammary Neoplasms, Experimental / Q000628:therapy*; D051379:Mice; D000072737:Myeloid-Derived Suppressor Cells / Q000166:cytology*; D009368:Neoplasm Transplantation; D016019:Survival Analysis; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D018840:HSP70 Heat-Shock Proteins