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靶向结直肠癌复发中的分子残留病灶与免疫逃逸:生物标志物指导的免疫治疗与细胞治疗

英文原题:Targeting molecular residual disease and immune escape in colorectal cancer recurrence: biomarker-guided immunotherapy and cell therapies.

查看英文原题

Targeting molecular residual disease and immune escape in colorectal cancer recurrence: biomarker-guided immunotherapy and cell therapies.

PubMed 2026/07/22(内容时间) Front Med (Lausanne) Q1 · IF 3.6(JCR 2025)

研究概要

结直肠癌(CRC)根治性治疗后复发仍是一项重大临床挑战。

中文摘要

结直肠癌(CRC)根治性治疗后的复发仍是重大临床挑战。传统术后风险分层依赖临床病理变量,而复发日益被视为由分子残留病灶(MRD)、免疫编辑、肿瘤微环境重塑及治疗耐药细胞状态所塑造的动态生物学过程。循环肿瘤DNA(ctDNA)已成为临床相关的MRD生物标志物,用于识别高复发风险患者并优化辅助治疗决策。与此同时,错配修复缺陷、微卫星不稳定性、肿瘤突变负荷、抗原呈递状态、T细胞耗竭、髓系抑制及空间免疫排斥等免疫生物标志物,决定了复发性疾病是否对免疫治疗敏感。本Mini Review探讨如何将MRD与免疫逃逸整合入生物标志物指导的复发性CRC框架。我们总结了支持ctDNA指导的复发监测、MSI-H/dMMR CRC中的免疫检查点阻断、靶向新抗原或突变KRAS的疫苗策略,以及包括CAR-T、CAR-NK和TCR工程化方法在内的工程化细胞疗法的近期证据。我们还讨论了可解释机器学习模型和基于SHAP的特征归因如何在模型经过严格外部验证的前提下,帮助优先筛选复发生物标志物并丰富临床试验。连接MRD检测、免疫谱分析和细胞治疗靶点选择的生物标志物指导策略,可能为复发性CRC更个体化的免疫干预提供一条转化路径。在此框架中,AI被定位为一个可审计的决策支持层,连接ctDNA动力学、免疫生物标志物域、细胞治疗资格和试验富集决策,而非作为自主的治疗选择器。

展开英文摘要原文

Colorectal cancer (CRC) recurrence after curative-intent treatment remains a major clinical challenge. Conventional postoperative risk stratification relies on clinicopathological variables, whereas recurrence is increasingly understood as a dynamic biological process shaped by molecular residual disease (MRD), immune editing, tumor microenvironmental remodeling and therapy-resistant cellular states. Circulating tumor DNA (ctDNA) has emerged as a clinically relevant MRD biomarker for identifying patients at high risk of relapse and for refining adjuvant-treatment decisions. At the same time, immune biomarkers such as mismatch repair deficiency, microsatellite instability, tumor mutational burden, antigen-presentation status, T-cell exhaustion, myeloid suppression and spatial immune exclusion determine whether recurrent disease is susceptible to immunotherapy. This Mini Review discusses how MRD and immune escape can be integrated into a biomarker-guided framework for recurrent CRC. We summarize recent evidence supporting ctDNA-guided recurrence surveillance, immune checkpoint blockade in MSI-H/dMMR CRC, vaccine-based strategies targeting neoantigens or mutant KRAS, and engineered cell therapies including CAR-T, CAR-NK and TCR-engineered approaches. We also discuss how interpretable machine-learning models and SHAP-based feature attribution may help prioritize recurrence biomarkers and enrich clinical trials, provided that models undergo rigorous external validation. A biomarker-guided strategy linking MRD detection, immune profiling and cell-therapy target selection may provide a translational pathway toward more individualized immune intervention for recurrent CRC. In this framework, AI is positioned as an auditable decision-support layer that links ctDNA kinetics, immune biomarker domains, cell-therapy eligibility, and trial-enrichment decisions rather than as an autonomous treatment selector.

论文信息

作者
Shan Y、Zhang X、Liu J、Hu B、Yang L、Wang H、Li J、Jiang Z
第一作者单位
The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.China
通讯作者单位
Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.China
文献类型
综述
期刊
Frontiers in medicine2026
原文标识
PubMed 42558893 · DOI 10.3389/fmed.2026.1906283