Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou 510060, P.R. China.
Med. 2024 Nov 8;5(11):1378-1392.e3. doi: 10.1016/j.medj.2024.07.006. Epub 2024 Jul 31.
Clinical trials support the efficacy of immune checkpoint blockades (ICBs) plus chemotherapy in a subset of patients with metastatic gastric cancer (mGC). To identify the determinants of response, we developed a TMEscore model to assess tumor microenvironment (TME), which was previously proven to be a biomarker for ICBs.
A reference database of TMEscore assays was established using PCR assay kits containing 30 TME genes. This multi-center prospective clinical trial (NCT#04850716) included patients with mGC who were administered ICB combined with chemotherapy as a first-line regimen. Eighty-six tumor samples extracted from five medical centers before treatment were used to estimate the TMEscore, PD-L1 (CPS), and mismatch repair deficiency.
The objective response rate (ORR) and median PFS of the cohort were 31.4% and six months. Enhanced ORR was observed in TMEscore-high mGC patients (ORR = 59%). The survival analysis demonstrated that high TMEscore was significantly associated with a more favorable PFS and OS. Moreover, TMEscore was found to be a predictive biomarker that surpassed MSI and CPS (AUC = 0.873, 0.511, and 0.524, respectively). By integrating the TMEscore and clinical variables, the fused model further enhances the predictive efficiency and translational application in a clinical setting.
This prospective clinical study indicates that the TMEscore assay is a robust biomarker for screening patients with mGC who may derive survival benefits from ICB plus chemotherapy.
Guangdong Basic and Applied Basic Research Foundation (2023A1515011214), Science and Technology Program of Guangzhou (202206080011), and Guangzhou Science and Technology Project (2023A03J0722 and 2023A04J2357).
临床试验支持免疫检查点阻断（ICB）联合化疗在转移性胃癌（mGC）患者亚组中的疗效。为了确定反应的决定因素，我们开发了一种 TMEscore 模型来评估肿瘤微环境（TME），该模型之前已被证明是 ICB 的生物标志物。
使用包含 30 个 TME 基因的 PCR 检测试剂盒建立了 TMEscore 检测的参考数据库。这项多中心前瞻性临床试验（NCT#04850716）纳入了接受 ICB 联合化疗作为一线方案治疗的 mGC 患者。从五个医疗中心提取的 86 个治疗前肿瘤样本用于估计 TMEscore、PD-L1（CPS）和错配修复缺陷。
该队列的客观缓解率（ORR）和中位 PFS 为 31.4%和 6 个月。TMEscore 高的 mGC 患者观察到增强的 ORR（ORR=59%）。生存分析表明，高 TMEscore 与更有利的 PFS 和 OS 显著相关。此外，TMEscore 被发现是一种预测生物标志物，超过了 MSI 和 CPS（AUC=0.873、0.511 和 0.524）。通过整合 TMEscore 和临床变量，融合模型进一步提高了预测效率，并在临床环境中具有更好的转化应用。
这项前瞻性临床研究表明，TMEscore 检测是筛选可能从 ICB 联合化疗中获益的 mGC 患者的一种强大的生物标志物。
广东省基础与应用基础研究基金（2023A1515011214）、广州市科技计划（202206080011）和广州市科技计划项目（2023A03J0722 和 2023A04J2357）。
