新辅助免疫疗法正在针对食管鳞状细胞癌（ESCC）进行深入研究。本研究评估新辅助免疫化疗 (nICT) 在 ESCC 中的疗效和免疫反应。在这项 II 期试验 (ChiCTR2100045722) 中，纳入了接受 nICT 的局部晚期 ESCC 患者。主要终点是病理完全缓解（pCR）率。通过多重免疫荧光、RNA-seq 和 TCR-seq 来探索 nICT 背后的免疫反应。总共入组 42 名患者，达到 27.0% 的 pCR 率。 1年、2年DFS和OS率分别为89.2%、64.4%和97.3%、89.2%。 RNA-seq 分析强调 T 细胞激活是最显着富集的途径。肿瘤免疫微环境 (TIME) 的特点是高 CD4、CD8、Foxp3 和 PD-L1 水平，与更好的病理消退 (TRS0/1) 相关。 TIME被分为免疫渗透型、免疫耐受型和免疫沙漠型。值得注意的是，免疫浸润类型和三级淋巴结构与改善的结果相关。在 nICT 背景下，TIM-3 对治疗效果产生负面影响，而 nICT 后 TIGIT/PD-1 表达升高与 CD8 T 细胞水平呈正相关。 TCR-seq 确定了三种 TCR 重排，强调了 T 细胞反应的特异性。新辅助卡瑞利珠单抗联合化疗对局部晚期、可切除的 ESCC 有效，引发与临床结果密切相关的深刻免疫反应。© 2024。作者。

Neoadjuvant immunotherapy is under intensive investigation for esophageal squamous cell carcinoma (ESCC). This study assesses the efficacy and immune response of neoadjuvant immunochemotherapy (nICT) in ESCC.In this phase II trial (ChiCTR2100045722), locally advanced ESCC patients receiving nICT were enrolled. The primary endpoint was the pathological complete response (pCR) rate. Multiplexed immunofluorescence, RNA-seq and TCR-seq were conducted to explore the immune response underlying nICT.Totally 42 patients were enrolled, achieving a 27.0% pCR rate. The 1-year, 2-year DFS and OS rates were 89.2%, 64.4% and 97.3%, 89.2%, respectively. RNA-seq analysis highlighted T-cell activation as the most significantly enriched pathway. The tumour immune microenvironment (TIME) was characterised by high CD4, CD8, Foxp3, and PD-L1 levels, associating with better pathological regression (TRS0/1). TIME was categorised into immune-infiltrating, immune-tolerant, and immune-desert types. Notably, the immune-infiltrating type and tertiary lymphoid structures correlated with improved outcomes. In the context of nICT, TIM-3 negatively influenced treatment efficacy, while elevated TIGIT/PD-1 expression post-nICT correlated positively with CD8+ T cell levels. TCR-seq identified three TCR rearrangements, underscoring the specificity of T-cell responses.Neoadjuvant camrelizumab plus chemotherapy is effective for locally advanced, resectable ESCC, eliciting profound immune response that closely associated with clinical outcomes.© 2024. The Author(s).