Colorectal cancer exosomes induce tumor associated macrophage polarization to inhibit the anti-tumor activity of CD8+T cells
10.12007/j.issn.0258-4646.2025.01.011
- VernacularTitle:结直肠癌外泌体诱导肿瘤相关巨噬细胞极化抑制CD8+T细胞抗肿瘤活性
- Author:
Jianghao ZHOU
1
;
Shuhai XIE
1
;
Yong CHEN
1
Author Information
1. 海南医科大学第一附属医院胃肠肿瘤外科,海口 570102
- Publication Type:Journal Article
- Keywords:
colorectal cancer;
exosome;
tumor associated macrophage;
CD8+T cell
- From:
Journal of China Medical University
2025;54(1):61-68
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of macrophage polarization induced by colorectal cancer exosomes on the anti-tumor activity of CD8+T cells.Methods M0 macrophages were co-incubated with PBS,HT-29 cells,and LoVo exosomes(HT-29 and LoVo exo)for 48 h,and termed the PBS,HT-29 exo,and LoVo exo groups.Real-time quantitative polymerase chain reaction was performed to detect M2 macrophage biomarker CD206,Arginase-1,IL-10,and CD163 mRNA expressions as well as M1 macrophage biomarker iNOS and IL-1β mRNA expressions.CD8+T-cells were co-incubated with the macrophages of the aforementioned groups(PBS+M0,HT-29 exo+M0,and LoVo exo+M0 groups)for 48 h.Flow cytometry was performed to detect CD8+T PD-1 expression.Next,the PBS+M0,HT-29 exo+M0,and LoVo exo+M0 groups of CD8+T-cells were incubated with HT-29 or LoVo cells for 24 h,respectively(PBS+M0/CD8+T,HT-29 exo+M0/CD8+T,and LoVo exo+M0/CD8+T groups).Subsequently,the enzyme-linked immunosorbent assay(ELISA)was used to detect the concentration of IFN-γ,perforin,and granzyme B in the cell supernatant.The cell lysis rates of HT-29 and LoVo cells were detected through cytotoxicity experiments.Results Compared with the PBS group,CD206,Arginase-1,IL-10,and CD 163 mRNA expressions of macrophages in the HT-29 exo and LoVo exo groups were significantly upregulated(P＜0.05),whereas iNOS and IL-1βmRNA expressions were significantly downregulated(P＜0.05).Compared with the PBS+M0 group,the HT-29 exo+M0 and LoVo exo+M0 groups exhibited significantly increased PD-1 expression(P＜0.05).Compared with the PBS+M0/CD8+T group,the IFN-γ,perforin,and granzyme B levels in the cell culture supernatant of the HT-29 exo+M0/CD8+T and LoVo exo+M0/CD8+T groups were significantly reduced(P＜0.05),and the cell lysis rates of HT-29 and LoVo were significantly reduced(P＜0.001).Conclusion M2 macrophage induced by HT-29 and LoVo exo can inhibit the tumor-killing function of CD8+T cells.
