Wang Kaifang, Cai Rong, Fei Shuting, Chen Xuzheng, Feng Sisi, Zhang Lulu, Liu Hui, Zhang Zhiguang, Song Jun, Zhou Ruixiang
The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; School of Dentistry, Shenzhen University Medical School, Shenzhen, China; Department of Biology, Faculty of Science, Hong Kong Baptist University, Hongkong, China.
The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.
Mol Cell Endocrinol. 2023 Jun 1;568-569:111917. doi: 10.1016/j.mce.2023.111917. Epub 2023 Apr 5.
Melatonin (MLT) is a hormone with potential anti-tumor properties, but the molecular mechanisms remain unclear. The present study aimed to explore the effect of MLT on exosomes derived from gastric cancer cells, with the goal of gaining insight into its anti-tumor activity. Results from in vitro experiments showed that MLT was able to enhance the anti-tumor activity of macrophages that had been suppressed by exosomes from gastric cancer cells. This effect was achieved through regulation of the levels of PD-L1 in macrophages via modulation of the associated microRNAs in the cancer-derived exosomes. Furthermore, MLT treatment increased the secretion of TNF-α and CXCL10 by the macrophages. Besides, MLT treatment of gastric cancer cells led to the production of exosomes that promoted the recruitment of CD8 T cells to the tumor site, resulting in inhibition of tumor growth. Collectively, these results provide evidence for the modulation of the tumor immune microenvironment by MLT through regulation of exosomes derived from gastric cancer cells, suggesting a potential role for MLT in novel anti-tumor immunotherapies.
褪黑素（MLT）是一种具有潜在抗肿瘤特性的激素，但其分子机制尚不清楚。本研究旨在探讨MLT对胃癌细胞来源外泌体的影响，以期深入了解其抗肿瘤活性。体外实验结果表明，MLT能够增强被胃癌细胞外泌体抑制的巨噬细胞的抗肿瘤活性。这种效应是通过调节癌症来源外泌体中相关微小RNA来调控巨噬细胞中PD-L1的水平实现的。此外，MLT处理增加了巨噬细胞分泌TNF-α和CXCL10。此外，用MLT处理胃癌细胞会导致外泌体的产生，这些外泌体促进CD8 T细胞募集到肿瘤部位，从而抑制肿瘤生长。总体而言，这些结果为MLT通过调节胃癌细胞来源的外泌体来调控肿瘤免疫微环境提供了证据，表明MLT在新型抗肿瘤免疫治疗中具有潜在作用。
