Department of Hematology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, 94305-5117, USA.
Mol Cancer. 2018 Feb 15;17(1):32. doi: 10.1186/s12943-018-0814-0.
Intratumor heterogeneity of tumor clones and an immunosuppressive microenvironment in cancer ecosystems contribute to inherent difficulties for tumor treatment. Recently, chimeric antigen receptor (CAR) T-cell therapy has been successfully applied in the treatment of B-cell malignancies, underscoring its great potential in antitumor therapy. However, functional challenges of CAR-T cell therapy, especially in solid tumors, remain. Here, we describe cancer-immunity phenotypes from a clonal-stromal-immune perspective and elucidate mechanisms of T-cell exhaustion that contribute to tumor immune evasion. Then we assess the functional challenges of CAR-T cell therapy, including cell trafficking and infiltration, targeted-recognition and killing of tumor cells, T-cell proliferation and persistence, immunosuppressive microenvironment and self-control regulation. Finally, we delineate tumor precision informatics and advancements in engineered CAR-T cells to counteract inherent challenges of the CAR-T cell therapy, either alone or in combination with traditional therapeutics, and highlight the therapeutic potential of this approach in future tumor precision treatment.
肿瘤克隆的肿瘤内异质性和癌症生态系统中的免疫抑制微环境导致肿瘤治疗存在固有困难。最近，嵌合抗原受体 (CAR) T 细胞疗法已成功应用于 B 细胞恶性肿瘤的治疗，突显了其在抗肿瘤治疗中的巨大潜力。然而，CAR-T 细胞疗法的功能挑战仍然存在，尤其是在实体肿瘤中。在这里，我们从克隆-基质-免疫的角度描述了癌症免疫表型，并阐明了导致肿瘤免疫逃逸的 T 细胞衰竭的机制。然后，我们评估了 CAR-T 细胞疗法的功能挑战，包括细胞迁移和浸润、靶向识别和杀伤肿瘤细胞、T 细胞增殖和持久性、免疫抑制微环境和自我控制调节。最后，我们描述了肿瘤精准信息学和工程 CAR-T 细胞的进展，以对抗 CAR-T 细胞疗法的固有挑战，无论是单独使用还是与传统疗法联合使用，并强调了该方法在未来肿瘤精准治疗中的治疗潜力。
