Chen Zhijun, Cao Kexin, Zhang Jinghang, Liu Zhuangzhuang, Lu Liaoxun, Qi Bo, Shi Lijin, Huang Rong, Zhao Song
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou,China.
Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang,China.
Curr Cancer Drug Targets. 2021;21(3):244-253. doi: 10.2174/1568009620666201120152333.
Esophageal squamous cell carcinoma (ESCC) is a major subtype of esophageal cancers. The five-year survival rate of ESCC is low, and molecular targets for ESCC treatment and prognosis assessment are very limited. T cells are critical for the clearance of cancer cells, and blockade of co-inhibitory molecules for T cell activation has emerged as a promising therapy to treat cancer patients. However, in ESCC patients, co-inhibitory molecules regulating T cell activation are poorly documented.
We aim to evaluate how the presence of inhibitory check-point molecules in T cells could impact the survival of patients.
We performed a follow-up study of 161 patients undergoing resection of esophageal carcinoma from February 2014 to December 2015, by immunohistochemical staining of six co-inhibitory molecules for T cell activation, namely PD-1, CTLA-4, TIM-3, LAG-3, BTLA and A2AR. Expression of each of the six co-inhibitory molecules was analyzed for its correlation with patient survival by Kaplan-Meier survival analysis. We also applied Kaplan-Meier analyses to evaluate the concomitant expression of co-inhibitory molecules and their correlation with patient survival.
We found that levels of PD-1, TIM-3 and BTLA can be used as independent prognostic factors for the overall survival of patients with ESCC. More importantly, our study found that the co-expression of PD-1 and TIM-3, PD-1 and BTLA, TIM-3 and BTLA significantly reduced the survival of patients with ESCC (P<0.05).
Therefore, our results suggest the necessity of evaluating the tumor tissue expression of co-inhibitory molecules and targeting co-expressed molecules in immunotherapies for ESCC patients.
食管鳞状细胞癌（ESCC）是食管癌的主要亚型。ESCC的五年生存率较低，用于ESCC治疗和预后评估的分子靶点非常有限。T细胞对于清除癌细胞至关重要，阻断共抑制分子以激活T细胞已成为治疗癌症患者的一种有前景的疗法。然而，在ESCC患者中，调节T细胞激活的共抑制分子的相关记录较少。
我们旨在评估T细胞中抑制性检查点分子的存在如何影响患者的生存。
我们对2014年2月至2015年12月期间接受食管癌切除术的161例患者进行了随访研究，通过免疫组织化学染色检测T细胞激活的六种共抑制分子，即程序性死亡受体1（PD-1）、细胞毒性T淋巴细胞相关蛋白4（CTLA-4）、T细胞免疫球蛋白黏蛋白分子3（TIM-3）、淋巴细胞活化基因3蛋白（LAG-3）、B和T淋巴细胞衰减蛋白（BTLA）以及腺苷A2A受体（A2AR）。通过Kaplan-Meier生存分析分析六种共抑制分子中每种分子的表达与患者生存的相关性。我们还应用Kaplan-Meier分析来评估共抑制分子的联合表达及其与患者生存的相关性。
我们发现PD-1、TIM-3和BTLA的水平可作为ESCC患者总生存的独立预后因素。更重要的是，我们的研究发现PD-1和TIM-3、PD-1和BTLA、TIM-3和BTLA的联合表达显著降低了ESCC患者的生存率（P<0.05）。
因此，我们的结果表明有必要评估共抑制分子在肿瘤组织中的表达，并在ESCC患者的免疫治疗中靶向联合表达的分子。
