He Huan, Song Zijing, Lin Siqi, Wang Yu, Wang Guixiang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangzhou, China.
Int Immunopharmacol. 2023 Apr;117:109944. doi: 10.1016/j.intimp.2023.109944. Epub 2023 Mar 3.
Natural killer (NK) cells are lymphocytes with important anti-tumour functions. Cellular metabolism is dynamically regulated in NK cells and strongly influences their responses. Myc is a key regulator of immune cell activity and function, but little is known about how Myc controls NK cell activation and function. In this study, we found that c-Myc is involved in the regulation of NK cell immune activity. In the development of colon cancer, the energy generation disorder of tumor cells promotes the plunder of polyamines of NK cells by tumor cells, resulting in the inhibition of NK cell c-Myc. After inhibition of c-Myc, glycolysis of NK cells was impaired, resulting in decreased killing activity. There are three main types of polyamines: putrescine (Put), spermidine (Spd) and spermine (Spm). We found that the NK cells could reverse the inhibition state of c-Myc and glycolysis energy supply disorder and recover the killing activity of NK cells after giving certain spermidine. These results suggest that polyamine content and glycolysis supply under the regulation of c-Myc play a crucial role in the immune activity of NK cells.
自然杀伤(NK)细胞是具有重要抗肿瘤功能的淋巴细胞。细胞代谢在NK细胞中受到动态调节,并强烈影响其反应。Myc是免疫细胞活性和功能的关键调节因子,但关于Myc如何控制NK细胞的活化和功能知之甚少。在本研究中,我们发现c-Myc参与NK细胞免疫活性的调节。在结肠癌发生过程中,肿瘤细胞的能量产生紊乱促使肿瘤细胞掠夺NK细胞的多胺,导致NK细胞c-Myc受到抑制。c-Myc被抑制后,NK细胞的糖酵解受损,导致杀伤活性降低。多胺主要有三种类型:腐胺(Put)、亚精胺(Spd)和精胺(Spm)。我们发现,给予一定量的亚精胺后,NK细胞可以逆转c-Myc的抑制状态和糖酵解能量供应紊乱,并恢复NK细胞的杀伤活性。这些结果表明,在c-Myc调节下的多胺含量和糖酵解供应在NK细胞的免疫活性中起关键作用。