Phase 2 trial of perioperative chemo-immunotherapy for gastro-esophageal adenocarcinoma: The role of M2 macrophage landscape in predicting response

作者：Thierry Alcindor, James Tankel, Pierre Fiset, Sanjima Pal, Touhid Opu, Michael K. Strasser, Mehrnoush Dehghani, Nicholas Bertos, Dongmei Zuo, Carmen Mueller, Jonathan Cools‐Lartigue, Marc P. Hickeson, Victoria Marcus, Sophie Camilleri‐Broët, Alan Spatz, Gertruda Evaristo, Mina S. Farag, Giovanni P. Artho, Arielle Elkrief, Ramy Saleh, Swneke Donovan Bailey, Morag Park, Sui Huang, Veena Sangwan, Lorenzo Edwin Ferri · 发表于：Cell Reports Medicine · 年份：2025 · DOI：10.1016/j.xcrm.2025.102045 · 被引用次数：10 · 研究领域：Esophageal Cancer Research and Treatment、Cancer Immunotherapy and Biomarkers、Gastric Cancer Management and Outcomes

We present the clinical results of a phase 2 trial combining neoadjuvant docetaxel, cisplatin, 5 Flourouracil, and the PD-L1 inhibitor avelumab in locally advanced gastro-esophageal adenocarcinoma (GEA). Fifty-one patients receive neoadjuvant therapy with 50 proceeding to surgery. Grade 3-4 adverse events occur in 40%; complete/major pathological response is found in 7/50 (14%) and 9/50 (18%), with 2-year disease-free survival of 67.5%. There is no correlation between tumor regression and PD-L1 or mismatch repair (MMR) status. Multiplex immunohistochemistry and longitudinal single-cell transcriptomic profiling reveal alterations in certain innate immune cell populations, particularly noting an M2-tumor-associated macrophage (M2-TAM) proliferation in non-responding tumors. These findings describe the effective nature of this treatment regimen for GEA and reveal associated features of the inflammatory milieux associated with response to chemo-immunotherapy. The specific character of the inflammatory environment in non-responders may, in the future, help personalize treatment. This study was registered at ClinicalTrials.gov (NCT03288350).