Phase 2 trial of perioperative chemo-immunotherapy for gastro-esophageal adenocarcinoma: The role of M2 macrophage landscape in predicting response.
Publication Title
Cell Rep Med
Document Type
Article
Publication Date
4-15-2025
Keywords
washington; isb
Abstract
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).
Area of Special Interest
Digestive Health
Area of Special Interest
Cancer
Specialty/Research Institute
Gastroenterology
Specialty/Research Institute
Oncology
Specialty/Research Institute
Institute for Systems Biology
DOI
10.1016/j.xcrm.2025.102045
