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结直肠癌中肿瘤浸润免疫细胞的独特特征及其与浸润强度的关联

Distinctive profiles of tumor-infiltrating immune cells and association with intensity of infiltration in colorectal cancer.

作者信息

Wu Yugang, Yuan Lei, Lu Qicheng, Xu Haiyan, He Xiaozhou

机构信息

Department of Surgery, The Third Affiliated Hospital of Soochow University/The First People's Hospital of Changzhou, Changzhou, Jiangsu 213000, P.R. China.

出版信息

Oncol Lett. 2018 Mar;15(3):3876-3882. doi: 10.3892/ol.2018.7771. Epub 2018 Jan 10.

DOI:10.3892/ol.2018.7771
PMID:29456737
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5795874/
Abstract

Tumor-infiltrating immune cells are heterogeneous and consist of characteristic compartments, including T helper (Th)1 and regulatory T (Treg) cells that exhibit distinctive biological functions. The present study investigated the profile of infiltrating immune cells from surgically removed tumor tissues from patients with colorectal cancer. The characteristic transcription factors of Th1 and Th2 cells, Treg cells, Th17 cells and T follicular helper (Tfh) cells were analyzed. The results demonstrated that a marked increased number of Treg cells presented in tumor infiltrates when compared with non-tumor adjacent tissues. An increased number of Th1 and Tfh cells existed in tumor infiltrates compared with non-tumorous adjacent tissues, while the infiltration of Th17 and Th2 cells was similar between tumor and non-tumor adjacent tissues. Furthermore, there were an increased number of Treg cells in tumors with low infiltration compared with those with high infiltration. The expression of CXC motif chemokine (CXC) receptor 3, CXC ligand (CXCL)L9 and CXCL10 was significantly increased on infiltrating T cells in tumors with high infiltration as compared with those with low infiltration. Macrophages exhibited a dominant M2 phenotype in tumor infiltrates of colorectal cancer, whereas a balanced M1 and M2 phenotype presented in macrophages from the peripheral blood. stimulation of macrophages isolated from tumor tissue of colorectal cancer with granulocyte macrophage colony-stimulating factor and lipopolysaccharide did not drive to an inflammatory phenotype. The results provide insights into the pattern of immune cell infiltration in Chinese patients with colorectal cancer. It may be beneficial that patients with colorectal cancer are screened for the defined profile along with the expression of CXCL9 and CXCL10 in order to achieve better efficacy in clinical applications of immune-based therapy, including anti-programmed cell death protein 1 therapy.

摘要

肿瘤浸润性免疫细胞具有异质性,由特征性亚群组成,包括具有独特生物学功能的辅助性T(Th)1细胞和调节性T(Treg)细胞。本研究调查了从结直肠癌患者手术切除的肿瘤组织中浸润免疫细胞的情况。分析了Th1和Th2细胞、Treg细胞、Th17细胞和滤泡辅助性T(Tfh)细胞的特征性转录因子。结果表明,与非肿瘤相邻组织相比,肿瘤浸润中Treg细胞数量显著增加。与非肿瘤相邻组织相比,肿瘤浸润中Th1和Tfh细胞数量增加,而肿瘤组织与非肿瘤相邻组织中Th17和Th2细胞的浸润情况相似。此外,低浸润肿瘤中的Treg细胞数量高于高浸润肿瘤。与低浸润肿瘤相比,高浸润肿瘤中浸润T细胞上CXC基序趋化因子(CXC)受体3、CXC配体(CXCL)9和CXCL10的表达显著增加。巨噬细胞在结直肠癌肿瘤浸润中表现出占主导地位的M2表型,而外周血巨噬细胞呈现M1和M2表型的平衡。用粒细胞巨噬细胞集落刺激因子和脂多糖刺激从结直肠癌肿瘤组织分离的巨噬细胞不会使其转变为炎症表型。这些结果为中国结直肠癌患者免疫细胞浸润模式提供了见解。对结直肠癌患者进行定义的免疫细胞谱以及CXCL9和CXCL10表达的筛查,可能有利于在包括抗程序性细胞死亡蛋白1治疗在内的免疫治疗临床应用中取得更好的疗效。