Xu Nan, Wu Zhonglin, Pan Jun, Xu Xiao, Wei Qiang
Zhejiang University School of Medicine, Hangzhou 310058, China.
Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou 310006, China.
Mol Ther Oncol. 2024 Sep 10;32(4):200872. doi: 10.1016/j.omton.2024.200872. eCollection 2024 Dec 19.
Malignant tumors of the digestive system have had a notoriously dismal prognosis throughout history. Immunotherapy, radiotherapy, surgery, and chemotherapy are the primary therapeutic approaches for digestive system cancers. The rate of recurrence and metastasis, nevertheless, remains elevated. As one of the immunotherapies, chimeric antigen receptor T cell (CAR-T) therapy has demonstrated a promising antitumor effect in hematologic cancer. Despite undergoing numerous clinical trials, the ineffective antitumor effect and adverse effects of CAR-T cell therapy in the treatment of digestive system cancers continue to impede its clinical translation. It is necessary to surmount the restricted options for targeting proteins, the obstacles that impede CAR-T cell infiltration into solid tumors, and the limited survival time . We examined and summarized the developments, obstacles, and countermeasures associated with CAR-T therapy in digestive system cancers. Emphasis was placed on the regulatory functions of potential antigen targets, the tumor microenvironment, and immune evasion in CAR-T therapy. Thus, our analysis has furnished an all-encompassing comprehension of CAR-T cell therapy in digestive system cancers, which will generate tremendous enthusiasm for subsequent in-depth research into CAR-T-based therapies in digestive system cancers.
纵观历史，消化系统恶性肿瘤的预后一直极为糟糕。免疫疗法、放射疗法、手术和化疗是消化系统癌症的主要治疗方法。然而，复发和转移率仍然居高不下。作为免疫疗法之一，嵌合抗原受体T细胞（CAR-T）疗法在血液系统癌症中已显示出有前景的抗肿瘤效果。尽管已经进行了大量临床试验，但CAR-T细胞疗法在治疗消化系统癌症时的无效抗肿瘤作用和不良反应仍在继续阻碍其临床转化。有必要克服靶向蛋白选择受限、阻碍CAR-T细胞浸润实体瘤的障碍以及有限的存活时间等问题。我们研究并总结了与消化系统癌症中CAR-T疗法相关的进展、障碍和对策。重点关注了潜在抗原靶点的调节功能、肿瘤微环境以及CAR-T疗法中的免疫逃逸。因此，我们的分析提供了对消化系统癌症中CAR-T细胞疗法的全面理解，这将为后续深入研究基于CAR-T的消化系统癌症治疗方法带来巨大热情。
