Activated NK cells reprogram MDSCs via NKG2D-NKG2DL and IFN-γ to modulate antitumor T-cell response after cryo-thermal therapy

• DOI: 10.1136/jitc-2022-005769
• Publication Date: 2022-12-15T14:49:47Z
• Authors: Peng Peng; Yue Lou; Shicheng Wang; Junjun Wang; Zelu Zhang; Peishan Du; Jiamin Zheng; Ping Liu; Lisa X Xu
• Keywords: NKG2D; Myeloid-derived Suppressor Cell; Cancer Immunotherapy

Myeloid-derived suppressor cells (MDSCs) can potently inhibit T-cell activity, promote growth and metastasis of tumor contribute to resistance immunotherapy. Targeting MDSCs alleviate their protumor functions immunosuppressive activities is intimately associated with cancer Natural killer (NK) engage in crosstalk multiple myeloid alter adaptive immune responses, triggering immunity. However, whether the NK-cell-MDSC interaction modulate response requires further study. Cryo-thermal therapy could induce maturation by creating an acute inflammatory environment elicit a CD4+ Th1-dominant response, but mechanism regulating this process remains unclear.NK were depleted NKG2D was blocked monoclonal antibodies vivo. MDSCs, NK T assessed flow cytometry isolated magnetic-activated cell sorting (MACS). cocultured determine immunological function. The transcriptional profiles measured qRT-PCR RNA-sequencing. Isolated MACS study viability regulated cells. TIMER used comprehensively examine immunological, clinical, genomic features tumors.NK-cell activation after cryo-thermal decreased MDSC accumulation reprogrammed toward mature phenotype antitumor Furthermore, we discovered that kill via NKG2D-NKG2DL axis interferon gamma (IFN-γ) NKG2D. In addition, dependent on NKG2D, which promoted major histocompatibility complex Ⅱ pathway MDSCs. High activated NK-cell infiltration level tumors positively correlated better clinical outcomes.Cryo-thermal induces effective immunity activating reprogram providing promising therapeutic strategy for