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[CXCL8通过诱导M2巨噬细胞浸润和抑制CD8 T细胞浸润在结直肠癌中产生免疫抑制微环境]

[CXCL8 generates an immunosuppressive microenvironment in colorectal cancer through induction of M2 macrophage infiltration and inhibition of CD8 T cell infiltration].

作者信息

Shao Ying, Lan Yan, Song Bing, Sun Jiaying, Yang Tao

机构信息

Department of Pathophysiology, Shanxi Medical University, School of Basic Medicine, Taiyuan 030001, China.

Department of Biochemistry and Molecular Biology, Shanxi Medical University, School of Basic Medicine, Taiyuan 030001, China.

出版信息

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2024 Oct;40(10):880-886.

PMID:39442986
Abstract

Objective To investigate the immunomodulatory effects of CXCL8 on the microenvironment in colorectal cancer (CRC). Methods Subcutaneous transplanted tumor model in BALB/c mice was established using CXCL8-overexpressing CT26, a murine CRC cell line . Tumor growth was monitored, and after three weeks of formation, the tumors were excised, and the spleens were harvested. Firstly, the tumor single-cell suspensions were prepared, and the infiltration of M2 macrophages and CD8 T cells in the tumor microenvironment were detected by flow cytometry. Additionally, the spleen single-cell suspensions were prepared and CD8 T cells were sorted. T cells were co-cultured with CXCL8-overexpressing CT26 cells in vitro, and the cytotoxicity assays were performed to evaluate the killing ability of T cells. Results Overexpression of CXCL8 promoted the growth of CRC transplanted tumors. Tumor overexpressing CXCL8 exhibited increased the infiltration of M2 macrophages and decreased the infiltration of CD8 T cells. However, overexpression of CXCL8 in CRC cells did not affect the cytotoxicity of CD8 T cells in vitro. Conclusion CXCL8-overexpressing CRC cells promoted the infiltration of M2 macrophages and inhibited CD8 T cell infiltration to generate an immunosuppressive microenvironment in CRC.

摘要

目的 探讨CXCL8对结直肠癌(CRC)微环境的免疫调节作用。方法 使用过表达CXCL8的小鼠结直肠癌细胞系CT26建立BALB/c小鼠皮下移植瘤模型。监测肿瘤生长,在肿瘤形成三周后,切除肿瘤并收获脾脏。首先,制备肿瘤单细胞悬液,通过流式细胞术检测肿瘤微环境中M2巨噬细胞和CD8 T细胞的浸润情况。此外,制备脾脏单细胞悬液并分选CD8 T细胞。将T细胞与过表达CXCL8的CT26细胞在体外共培养,并进行细胞毒性试验以评估T细胞的杀伤能力。结果 CXCL8的过表达促进了结直肠癌移植瘤的生长。过表达CXCL8的肿瘤显示M2巨噬细胞浸润增加,CD8 T细胞浸润减少。然而,结直肠癌细胞中CXCL8的过表达在体外不影响CD8 T细胞的细胞毒性。结论 过表达CXCL8的结直肠癌细胞促进M2巨噬细胞浸润并抑制CD8 T细胞浸润,从而在结直肠癌中产生免疫抑制微环境。

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