Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Department of Medical Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Biomed Pharmacother. 2024 Sep;178:117229. doi: 10.1016/j.biopha.2024.117229. Epub 2024 Aug 2.
Enormous patients with gastric cancer (GC) are insensitive to chemotherapy and targeted therapy without the chance of radical surgery, so immunotherapy may supply a novel choice for them. Chimeric antigen receptor (CAR)-T cell therapy has the advantages of higher specificity, stronger lethality, and longer-lasting efficacy, and it has the potential for GC in the future. However, its application still faces numerous obstacles in terms of accuracy, efficacy, and safety. Cytokines can mediate the migration, proliferation, and survival of immune cells, regulate the duration and strength of immune responses, and are involved in the occurrence of severe side effects in CAR-T cell therapy. The expression levels of specific cytokines are associated with the genesis, invasion, metastasis, and prognosis of GC. Applications of cytokines and their receptors in CAR-T cell therapy have emerged, and various cytokines and their receptors have contributed to improving CAR-T cell anti-tumor capabilities. Large amounts of central cytokines in this therapy include chemokines, interleukins (ILs), transforming growth factor-β (TGF-β), and colony-stimulating factors (CSFs). Meanwhile, researchers have explored the combination therapy in treating GC, and several approaches applied to other malignancies can also be considered as references. Therefore, our review comprehensively outlines the biological functions and clinical significance of cytokines and summarizes current advances and innovative strategies for harnessing cytokines to optimize CAR-T cell therapy for GC.
大量患有胃癌（GC）的患者对化疗和靶向治疗不敏感，没有根治性手术的机会，因此免疫疗法可能为他们提供新的选择。嵌合抗原受体（CAR）-T 细胞疗法具有更高的特异性、更强的杀伤力和更长的疗效持久力，有望成为未来治疗 GC 的方法。然而，其应用在准确性、疗效和安全性方面仍面临诸多障碍。细胞因子可以调节免疫细胞的迁移、增殖和存活，调节免疫反应的持续时间和强度，并参与 CAR-T 细胞治疗中严重副作用的发生。特定细胞因子的表达水平与 GC 的发生、侵袭、转移和预后有关。细胞因子及其受体在 CAR-T 细胞治疗中的应用已经出现，各种细胞因子及其受体有助于提高 CAR-T 细胞的抗肿瘤能力。该疗法中大量的中枢细胞因子包括趋化因子、白细胞介素（ILs）、转化生长因子-β（TGF-β）和集落刺激因子（CSFs）。同时，研究人员还探索了联合治疗 GC 的方法，其他恶性肿瘤中应用的几种方法也可以作为参考。因此，我们的综述全面概述了细胞因子的生物学功能和临床意义，并总结了利用细胞因子优化 CAR-T 细胞治疗 GC 的最新进展和创新策略。
