{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T15:12:34Z","timestamp":1775920354246,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key R&amp;D Program of China","award":["2023YFC2411403"],"award-info":[{"award-number":["2023YFC2411403"]}]},{"name":"National Key R&amp;D Program of China","award":["2020YFA0909003"],"award-info":[{"award-number":["2020YFA0909003"]}]},{"name":"National Key R&amp;D Program of China","award":["82072085"],"award-info":[{"award-number":["82072085"]}]},{"name":"National Key R&amp;D Program of China","award":["24Z510800596"],"award-info":[{"award-number":["24Z510800596"]}]},{"name":"National Key R&amp;D Program of China","award":["ZJ2021-ZD-007"],"award-info":[{"award-number":["ZJ2021-ZD-007"]}]},{"name":"National Natural Science Foundation of China","award":["2023YFC2411403"],"award-info":[{"award-number":["2023YFC2411403"]}]},{"name":"National Natural Science Foundation of China","award":["2020YFA0909003"],"award-info":[{"award-number":["2020YFA0909003"]}]},{"name":"National Natural Science Foundation of China","award":["82072085"],"award-info":[{"award-number":["82072085"]}]},{"name":"National Natural Science Foundation of China","award":["24Z510800596"],"award-info":[{"award-number":["24Z510800596"]}]},{"name":"National Natural Science Foundation of China","award":["ZJ2021-ZD-007"],"award-info":[{"award-number":["ZJ2021-ZD-007"]}]},{"name":"Shanghai Science and Technology Commission of Shanghai Municipality","award":["2023YFC2411403"],"award-info":[{"award-number":["2023YFC2411403"]}]},{"name":"Shanghai Science and Technology Commission of Shanghai Municipality","award":["2020YFA0909003"],"award-info":[{"award-number":["2020YFA0909003"]}]},{"name":"Shanghai Science and Technology Commission of Shanghai Municipality","award":["82072085"],"award-info":[{"award-number":["82072085"]}]},{"name":"Shanghai Science and Technology Commission of Shanghai Municipality","award":["24Z510800596"],"award-info":[{"award-number":["24Z510800596"]}]},{"name":"Shanghai Science and Technology Commission of Shanghai Municipality","award":["ZJ2021-ZD-007"],"award-info":[{"award-number":["ZJ2021-ZD-007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In our previous studies, a novel cryothermal therapy (CTT) was developed to induce systemic long-term anti-tumor immunity. Natural killer (NK) cells were found to play an important role in CTT-induced long-term immune-mediated tumor control at the late stage after CTT, but the underlying mechanism is unclear. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that have potent immunosuppressive effects on T cells and weaken the long-term benefits of immunotherapy. Consequently, overcoming MDSC immunosuppression is essential for maintaining the long-term efficacy of immunotherapy. In this study, we revealed that NK cells considerably diminish MDSC accumulation at the late stage after CTT, boost T cell production, increase T cell activation, and promote MDSC maturation, culminating in Th1-dominant CD4+ T cell differentiation and enhancing NK and CD8+ T cell cytotoxicity. Additionally, NK cells activate ERK signaling in MDSCs through NKG2D-ligand interaction to increase the activity of tumor necrosis factor (TNF)-\u03b1 converting enzyme (TACE)-cleaved membrane TNF-\u03b1. Furthermore, Increased TACE activity releases more soluble TNF-\u03b1 from MDSCs to promote MDSC maturation. In our studies, we propose a novel mechanism by which NK cells can overcome MDSC-induced immunosuppression and maintain CTT-induced persistent anti-tumor immunity, providing a prospective therapeutic option to improve the performance of cancer immunotherapy.<\/jats:p>","DOI":"10.3390\/ijms25105151","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T05:16:45Z","timestamp":1715231805000},"page":"5151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Natural Killer Cells Reprogram Myeloid-Derived Suppressor Cells to Induce TNF-\u03b1 Release via NKG2D\u2013Ligand Interaction after Cryo-Thermal Therapy"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8747-4083","authenticated-orcid":false,"given":"Jiaqi","family":"You","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shicheng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongxin","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zelu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjun","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Lou","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yichen","family":"Yao","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuankai","family":"Hao","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"72167","DOI":"10.18632\/oncotarget.20050","article-title":"Small-molecule inhibitors of PD-1\/PD-L1 immune checkpoint alleviate the PD-L1-induced exhaustion of T-cells","volume":"8","author":"Skalniak","year":"2017","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e005769","DOI":"10.1136\/jitc-2022-005769","article-title":"Activated NK cells reprogram MDSCs via NKG2D-NKG2DL and IFN-\u03b3 to modulate antitumor T-cell response after cryo-thermal therapy","volume":"10","author":"Peng","year":"2022","journal-title":"J. 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