文章目录

食管癌新辅助治疗中的进化和免疫微环境动力学

原文发布日期：2025-05-14

英文摘要：

摘要翻译：

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文章：

食管癌新辅助治疗中的进化和免疫微环境动力学

Evolutionary and immune microenvironment dynamics during neoadjuvant treatment of esophageal adenocarcinoma

原文发布日期：2025-05-14

英文摘要：

Locally advanced esophageal adenocarcinoma remains difficult to treat and the ecological and evolutionary dynamics responsible for resistance and recurrence are incompletely understood. Here, we performed longitudinal multiomic analysis of patients with esophageal adenocarcinoma in the MEMORI trial. Multi-region multi-timepoint whole-exome and paired transcriptome sequencing was performed on 27 patients before, during and after neoadjuvant treatment. We found major transcriptomic changes during treatment with upregulation of immune, stromal and oncogenic pathways. Genetic data revealed that clonal sweeps through treatment were rare. Imaging mass cytometry and T cell receptor sequencing revealed remodeling of the tumor microenvironment during treatment. The presence of genetic immune escape, a less-cytotoxic T cell phenotype and a lack of clonal T cell expansions were linked to poor treatment response. In summary, there were widespread transcriptional and environmental changes through treatment, with limited clonal replacement, suggestive of phenotypic plasticity.

摘要翻译：

结食管腺癌的局部进展性阶段仍难以治疗，而导致其抗药性和复发的生态和进化动力学尚不完全理解。在这里，我们对 MEMORI 试验中的结食管腺癌患者进行了纵向多组分析。我们在27名受试者治疗前、中和后分别进行了多区域多时间点全外显子和配对转录组测序。我们发现，在治疗过程中转录组发生了重大变化，包括免疫、stromal 和肿瘤ogenic 通路的上调。基因数据表明克隆突变罕见。成像 mass cytometry 和 T 细胞受体测序揭示了治疗期间肿瘤微环境的重塑。遗传免疫力逃避、较少的T细胞毒性以及缺乏克隆性T细胞扩展的存在与较差的治疗反应相关联。总之，治疗过程中有广泛的转录和环境变化，但克隆替代有限，这提示表型弹性的存在。