可切除局部晚期食管鳞癌新辅助卡瑞利珠单抗联合化疗的临床疗效和免疫应答：一项 2 期试验。

Clinical efficacy and immune response of neoadjuvant camrelizumab plus chemotherapy in resectable locally advanced oesophageal squamous cell carcinoma: a phase 2 trial.

机构信息

Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Department of Oncology, Guangzhou First People's Hospital, School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China.

出版信息

Br J Cancer. 2024 Oct;131(7):1126-1136. doi: 10.1038/s41416-024-02805-5. Epub 2024 Aug 20.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

Neoadjuvant camrelizumab plus chemotherapy is effective for locally advanced, resectable ESCC, eliciting profound immune response that closely associated with clinical outcomes.

背景

新辅助免疫疗法正在被深入研究用于治疗食管鳞癌（ESCC）。本研究评估了新辅助免疫化疗（nICT）在 ESCC 中的疗效和免疫应答。

方法

这是一项 II 期临床试验（ChiCTR2100045722），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 相关的免疫应答。

结果

共纳入 42 例患者，pCR 率为 27.0%。1 年、2 年无病生存（DFS）和总生存（OS）率分别为 89.2%、64.4%和 97.3%、89.2%。RNA-seq 分析突出了 T 细胞激活作为最显著富集的通路。肿瘤免疫微环境（TIME）的特征是 CD4、CD8、Foxp3 和 PD-L1 水平高，与更好的病理缓解（TRS0/1）相关。TIME 可分为免疫浸润型、免疫耐受型和免疫荒漠型。值得注意的是，免疫浸润型和三级淋巴结构与改善的结局相关。在 nICT 背景下，TIM-3 对治疗效果有负面影响，而 nICT 后 TIGIT/PD-1 表达的升高与 CD8+T 细胞水平呈正相关。TCR-seq 鉴定了三个 TCR 重排，突出了 T 细胞反应的特异性。