Colorectal Cancer-Derived Small Extracellular Vesicles Promote Tumor Immune Evasion by Upregulating PD-L1 Expression in Tumor-Associated Macrophages, Advanced science, 2022. (IF: 14.3 )

Abstract: In the tumor microenvironment of colorectal cancer (CRC), tumor-associated macrophages (TAMs) are one of the most abundant cell types and play an important role in the development of CRC, but the mechanism of interaction between them and cancer cells is not fully understood. This study revealed that CRC cells can secrete small extracellular vesicles (sEVs), which, when taken up by macrophages, promote M2-like polarization and the expression of PD-L1, thereby increasing the number of PD-L1^+CD206^+ macrophage subpopulations and reducing the activity of T cells. Furthermore, miR-21-5p and miR-200a in sEVs are key signaling molecules that regulate the impact of CRC on macrophages. These miRNAs, by regulating the PTEN/AKT and SCOS1/STAT1 signaling pathways, synergistically promote M2-like polarization and PD-L1 expression in macrophages, thereby inhibiting the activity of CD8 T cells and promoting tumor growth.

摘要：在结直肠癌（CRC）的肿瘤微环境中，肿瘤相关巨噬细胞（TAMs）是数量最多的细胞类型之一，在CRC的发展中扮演着重要角色，但它们与癌细胞之间的相互作用机制尚不完全清楚。本研究揭示了CRC细胞能够分泌小细胞外囊泡（sEVs），这些sEVs被巨噬细胞摄取后，会促进M2样极化和PD-L1的表达，从而增加PD-L1CD206巨噬细胞亚群的数量并降低T细胞的活性。此外，sEV中的miR-21-5p和miR-200a是调控CRC对巨噬细胞影响的关键信号分子。这些miRNA通过调控PTEN/AKT和SCOS1/STAT1信号途径，协同促进巨噬细胞的M2样极化和PD-L1表达，进而抑制CD8 T细胞的活性并促进肿瘤生长。