In this phase II study, 47 patients with locally advanced, resectable esophageal squamous cell carcinoma (ESCC) received three cycles of pembrolizumab plus chemotherapy, followed by Da Vinci robot-assisted surgery. The primary endpoints were safety and major pathological response (MPR). Key secondary endpoints included complete pathological response (pCR) and survival. No grade ≥3 adverse events or surgical delays occurred during neoadjuvant therapy. Among 46 patients studied for efficacy, the MPR and pCR rates were 72% and 41%, respectively. After a median follow-up of 27.2 months, the 2-year overall survival (OS) and disease-free survival (DFS) rates were 91% and 89%, respectively. Expansion of TRGC2⁺ NKT cells in peripheral blood correlated with neoadjuvant treatment effectiveness, which was validated by in vitro organoid experiments and external cancer datasets, and its functional classification and mechanism of action were further explored. These findings show preoperative pembrolizumab plus chemotherapy is a promising therapeutic strategy for resectable ESCC.

中文翻译：

---

新辅助 pembrolizumab 联合化疗治疗可切除食管鳞状细胞癌的前瞻性研究：Keystone-001 试验


在这项 II 期研究中，47 名局部晚期可切除食管鳞状细胞癌 （ESCC） 患者接受了三个周期的帕博利珠单抗联合化疗，然后接受了达芬奇机器人辅助手术。主要终点是安全性和主要病理反应 （MPR）。关键次要终点包括完全病理缓解 （pCR） 和生存率。新辅助治疗期间未发生 ≥3 级不良事件或手术延误。在研究疗效的 46 例患者中，MPR 和 pCR 率分别为 72% 和 41%。中位随访 27.2 个月后，2 年总生存率 （OS） 和无病生存率 （DFS） 分别为 91% 和 89%。TRGC2 ⁺ NKT 细胞在外周血中的扩增与新辅助治疗效果相关，这一点通过 体外类器官实验和外部癌症数据集得到验证，并进一步探索其功能分类和作用机制。这些发现表明，术前 pembrolizumab 联合化疗是可切除 ESCC 的一种有前途的治疗策略。