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

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-04-15 DOI:10.1016/j.xcrm.2025.102045

Thierry Alcindor, James Tankel, Pierre-Olivier Fiset, Sanjima Pal, Touhid Opu, Michael Strasser, Mehrnoush Dehghani, Nicholas Bertos, Dongmei Zuo, Carmen Mueller, Jonathan Cools-Lartigue, Marc Hickeson, Victoria Marcus, Sophie Camilleri-Broet, Alan Spatz, Gertruda Evaristo, Mina Farag, Giovanni Artho, Arielle Elkrief, Ramy Saleh, Swneke Bailey, Morag Park, Sui Huang, Veena Sangwan, Lorenzo Ferri

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引用次数: 0

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).

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胃食管腺癌围手术期化疗免疫治疗二期试验：M2巨噬细胞景观在预测反应中的作用。

我们提出了一项联合新辅助多西紫杉醇、顺铂、5 -氟尿嘧啶和PD-L1抑制剂avelumab治疗局部晚期胃食管腺癌（GEA）的2期试验的临床结果。51例患者接受新辅助治疗，50例进行手术。3-4级不良事件发生率为40%；完全/主要病理反应分别为7/50（14%）和9/50(18%)，2年无病生存率为67.5%。肿瘤消退与PD-L1或错配修复（MMR）状态没有相关性。多重免疫组织化学和纵向单细胞转录组分析揭示了某些先天免疫细胞群的改变，特别是在无反应的肿瘤中注意到m2 -肿瘤相关巨噬细胞（M2-TAM）的增殖。这些发现描述了GEA治疗方案的有效性，并揭示了与化学免疫治疗反应相关的炎症环境的相关特征。在未来，无应答者炎症环境的特殊性可能有助于个性化治疗。该研究已在ClinicalTrials.gov注册（NCT03288350）。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.