Huang Ping, Zhao Manyi, Xia Jianhong, Li Hongliang, Sun Junxia, Li Xin, Yang Chunsheng, Gao Guangyi, Zhou Wenhang, Zhong Meifeng, Yong Hongmei
Department of Medical Oncology, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, Jiangsu, China.
Department of Radiation Oncology, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, Jiangsu, China.
Front Immunol. 2025 May 13;16:1569042. doi: 10.3389/fimmu.2025.1569042. eCollection 2025.
Due to the low efficacy rates, effective biomarkers are desperately needed to determine populations of advanced esophageal squamous cell carcinoma (ESCC) that may benefit from immune checkpoint inhibitor (ICI) treatment.
To explore the relationship between IL-6 and the esophageal cancer tumor immune microenvironment using online databases and esophageal cancer tissue microarrays and to investigate the predictive role of IL-6 for immunotherapy in esophageal squamous carcinoma patients through clinical study data.
RNA-seq datasets of ESCC patients were obtained from TCGA, and the relationship between IL-6 and immune cells was discovered using TIMER 2.0 databases. CD8, IL-6, and PD-L1 expression in ESCC tissue microarrays were measured using immunohistochemistry, and then the tumor microenvironment was classified. Furthermore, blood specimens were collected from advanced ESCC patients before they received PD-1 inhibitors, and follow-up was conducted to gather clinical survival data. Based on IL-6 levels. We divided the population into the high and low IL-6 groups, comparing the efficacy and survival of the two groups.
IL-6 positively correlated with mRNA levels of PD-L1, negatively correlated with immune cells, and positively correlated with immunosuppressive cells. High IL-6 expression in tissues might make PD-1/L1 blockade therapy less effective. Individuals with higher baseline plasma IL-6 levels had significantly lower objective remission rates and inferior PFS and OS. Elevated baseline IL-6 was demonstrated to be an independent risk factor for the prognosis of advanced ESCC patients using PD-1 inhibitors, according to COX regression analysis.
IL-6 overexpression correlates with the immunosuppressive tumor microenvironment in ESCC, and it can be a predictive biomarker in ESCC patients received with PD-1 inhibitors.
由于有效率较低，迫切需要有效的生物标志物来确定可能从免疫检查点抑制剂（ICI）治疗中获益的晚期食管鳞状细胞癌（ESCC）人群。
利用在线数据库和食管癌组织芯片探讨白细胞介素-6（IL-6）与食管癌肿瘤免疫微环境之间的关系，并通过临床研究数据研究IL-6对食管鳞癌患者免疫治疗的预测作用。
从癌症基因组图谱（TCGA）获取ESCC患者的RNA测序数据集，并使用TIMER 2.0数据库发现IL-6与免疫细胞之间的关系。采用免疫组织化学法检测ESCC组织芯片中CD8、IL-6和程序性死亡受体配体1（PD-L1）的表达，然后对肿瘤微环境进行分类。此外，在晚期ESCC患者接受程序性死亡蛋白1（PD-1）抑制剂治疗前采集血液标本，并进行随访以收集临床生存数据。根据IL-6水平，将人群分为IL-6高表达组和低表达组，比较两组的疗效和生存率。
IL-6与PD-L1的mRNA水平呈正相关，与免疫细胞呈负相关，与免疫抑制细胞呈正相关。组织中IL-6高表达可能使PD-1/L1阻断治疗效果降低。基线血浆IL-6水平较高的个体客观缓解率显著较低，无进展生存期（PFS）和总生存期（OS）较差。COX回归分析表明，基线IL-6升高是晚期ESCC患者接受PD-1抑制剂治疗预后的独立危险因素。
IL-6过表达与ESCC免疫抑制性肿瘤微环境相关，它可能是接受PD-1抑制剂治疗的ESCC患者的预测生物标志物。
