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Natural Killer Cells Reprogram Myeloid-Derived Suppressor Cells to Induce TNF-α Release via NKG2D-Ligand Interaction after Cryo-Thermal Therapy.
You, Jiaqi; Wang, Shicheng; Zhu, Yongxin; Zhang, Zelu; Wang, Junjun; Lou, Yue; Yao, Yichen; Hao, Yuankai; Liu, Ping.
Afiliação
  • You J; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Wang S; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Zhu Y; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Zhang Z; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Wang J; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Lou Y; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Yao Y; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Hao Y; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Liu P; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
Int J Mol Sci ; 25(10)2024 May 09.
Article em En | MEDLINE | ID: mdl-38791188
ABSTRACT
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)-α converting enzyme (TACE)-cleaved membrane TNF-α. Furthermore, Increased TACE activity releases more soluble TNF-α 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Matadoras Naturais / Fator de Necrose Tumoral alfa / Subfamília K de Receptores Semelhantes a Lectina de Células NK / Células Supressoras Mieloides Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Matadoras Naturais / Fator de Necrose Tumoral alfa / Subfamília K de Receptores Semelhantes a Lectina de Células NK / Células Supressoras Mieloides Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article