TIM-3 was originally identified as a negative regulator of helper T cells and is expressed on dendritic cells (DCs). Since the inhibition of TIM-3 on DCs has been suggested to enhance T cell-mediated anti-tumor immunity, we examined its expression on DCs within the tumor microenvironment (TME) in colorectal cancer (CRC) using transcriptomic data from a public database (n= 592) and immunohistochemical evaluations from our cohorts of CRC (n= 115). The expression of TIM-3 on DCs in vitro was examined by flow cytometry, while the expression of its related molecules, cGAS and STING, on immature and mature DCs was assessed by Western blotting. The expression ofHAVCR2(TIM-3) was strongly associated with the infiltration of DCs within the TME of CRC. Immunohistochemical staining of clinical tissue samples revealed that tumor-infiltrating DCs expressed TIM-3; however, their number at the tumor-invasive front significantly decreased with stage progression. TIM-3 expression was higher on immature DCs than on mature DCs from several different donors (n= 6). Western blot analyses showed that the expression of STING was higher on mature DCs than on immature DCs, which was opposite to that of TIM-3. We demonstrated that TIM-3 was highly expressed on tumor-infiltrating DCs of CRC and that its expression was higher on immature DCs than on mature DCs.
TIM-3最初被鉴定为辅助性T细胞的负向调节因子，并在树突状细胞（DCs）上表达。鉴于抑制DCs上的TIM-3可增强T细胞介导的抗肿瘤免疫，我们利用公共数据库的转录组数据（n=592）及结直肠癌（CRC）患者队列（n=115）的免疫组织化学评估，检测了TIM-3在CRC肿瘤微环境（TME）内DCs上的表达情况。通过流式细胞术检测体外培养DCs上TIM-3的表达，同时采用蛋白质印迹法分析其相关分子cGAS和STING在未成熟与成熟DCs上的表达水平。结果显示，HAVCR2（TIM-3）的表达与CRC肿瘤微环境中DCs的浸润程度密切相关。临床组织样本的免疫组化染色显示，肿瘤浸润性DCs表达TIM-3，但其在肿瘤侵袭前沿的数量随肿瘤分期的进展显著减少。来自不同供体（n=6）的未成熟DCs上TIM-3表达量高于成熟DCs。蛋白质印迹分析表明，STING在成熟DCs上的表达高于未成熟DCs，这与TIM-3的表达模式相反。本研究证实TIM-3在CRC肿瘤浸润性DCs中高表达，且在未成熟DCs上的表达水平高于成熟DCs。
肿瘤(癌症)患者之家