白细胞介素8
CD8型
医学
癌症研究
细胞毒性T细胞
T细胞
免疫学
免疫系统
肿瘤微环境
白细胞介素10
流式细胞术
结直肠癌
细胞因子
癌症
生物
体外
内科学
生物化学
作者
Chao Zhao,Dan Wang,Zhen Li,Zhen Zhang,Yujie Xu,Zhibin Wang,Qingyang Lei,Dong Hun Han,Yachang Huo,Shasha Li,Ling Li,Yi Zhang
标识
DOI:10.1016/j.intimp.2023.110457
摘要
T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) is a vital immune checkpoint that regulates the immune response. However, the specific role of TIM3 in patients with colorectal cancer (CRC) have rarely been studied. In this study, we investigated the effect of TIM3 on CD8+ T cells in CRC and explored the mechanism of TIM3 regulation in tumor microenvironment (TME).Peripheral blood and tumor tissues of patients with CRC were collected to evaluate TIM3 expression using flow cytometry. Cytokines in the serum of healthy donors and patients with early- and advanced-stage CRC were screened using a multiplex assay. The effects of interleukin-8 (IL8) on TIM3 expression on CD8+ T cells were analyzed using cell incubation experiments in vitro. The correlation between TIM3 or IL8 and prognosis was verified using bioinformatics analysis.TIM3 expression on CD8+ T cells was obviously reduced in patients with advanced-stage CRC, whereas a lower TIM3 expression level was associated with poorer prognosis. Macrophage-derived IL8, which could inhibit TIM3 expression on CD8+ T cells, was significantly increased in the serum of patients with advanced CRC. In addition, the function and proliferation of CD8+ and TIM3+CD8+ T cells were inhibited by IL8, which was partly depending on TIM3 expression. The inhibitory effects of IL8 were reversed by anti-IL8 and anti-CXCR2 antibodies.In summary, macrophages-derived IL8 suppresses TIM3 expression on CD8+ T cells through CXCR2. Targeting the IL8/CXCR2 axis may be an effective strategy for treating patients with advanced CRC.
科研通智能强力驱动
Strongly Powered by AbleSci AI