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

• Published in: British journal of cancer 2024-10, Vol.131 (7), p.1126-1136
• Main Authors: Chen, Yue-Yun, Wang, Pei-Pei, Hu, Yang, Yuan, Yong, Yang, Yu-Shang, Shi, Hua-Shan, Hao, Qing, Lin, Zhen, Tian, Jiang-Fang, Zheng, Yue, Liu, Ting, Lin, Pan-Pan, Xu, Heng, Ma, Xue-Lei, Yang, Li, Ding, Zhen-Yu
• Format: Article
• Language: English
• Subjects: 631/67/1059/2325; 631/67/327; 692/4028/67/1504/1477; Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cancer Research; CD4 antigen; CD8 antigen; Cell activation; Chemotherapy; Drug Resistance; Epidemiology; Esophageal cancer; Esophageal carcinoma; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - immunology; Esophageal Neoplasms - pathology; Esophageal Squamous Cell Carcinoma - drug therapy; Esophageal Squamous Cell Carcinoma - immunology; Esophageal Squamous Cell Carcinoma - pathology; Female; Foxp3 protein; Humans; Immunofluorescence; Immunotherapy; Immunotherapy - methods; Lymphocytes T; Male; Microenvironments; Middle Aged; Molecular Medicine; Neoadjuvant Therapy; Oncology; Patients; PD-1 protein; PD-L1 protein; Squamous cell carcinoma; T cell receptors; Treatment Outcome; Tumor Microenvironment - immunology
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-024-02805-5

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.