1. Clinical efficacy and immune response of neoadjuvant camrelizumab plus chemotherapy in resectable locally advanced oesophageal squamous cell carcinoma: a phase 2 trial.
- Author
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Chen YY, Wang PP, Hu Y, Yuan Y, Yang YS, Shi HS, Hao Q, Lin Z, Tian JF, Zheng Y, Liu T, Lin PP, Xu H, Ma XL, Yang L, and Ding ZY
- Subjects
- Humans, Female, Male, Middle Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Aged, Treatment Outcome, Adult, Immunotherapy methods, Neoadjuvant Therapy, Esophageal Squamous Cell Carcinoma drug therapy, Esophageal Squamous Cell Carcinoma immunology, Esophageal Squamous Cell Carcinoma pathology, Esophageal Neoplasms drug therapy, Esophageal Neoplasms immunology, Esophageal Neoplasms pathology, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized therapeutic use, Tumor Microenvironment immunology
- Abstract
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., (© 2024. The Author(s).)
- Published
- 2024
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