决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Targeting molecular residual disease and immune escape in colorectal cancer recurrence: biomarker-guided immunotherapy and cell therapies.
Targeting molecular residual disease and immune escape in colorectal cancer recurrence: biomarker-guided immunotherapy and cell therapies.
结直肠癌(CRC)根治性治疗后复发仍是一项重大临床挑战。
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。
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.
MEMBER ACCOUNT
登录成功会直接打开下一页。