嵌合抗原受体(CAR)-T 细胞疗法是一种前沿的、有效的、快速发展的过继细胞免疫疗法。 CAR-T 细胞可以独立 识别肿瘤细胞的表面抗原,而不受主要组织相容性复合体的限制,从而减少了肿瘤细胞主要组织相容性复合体(MHC)相关抗 原呈递缺失导致的免疫逃逸。 尽管它已经被应用于血液系统恶性肿瘤并取得了令人瞩目的成果,但其在实体瘤的治疗应用 上仍然受到一些不利因素的影响。 其中一个因素是新陈代谢,这是一组基本的细胞过程,不仅维持细胞的生存和增殖,还作 为细胞适应其局部环境的手段。 肿瘤微环境内肿瘤细胞代谢会产生对碳水化合物和氨基酸等营养素的大量竞争,加上免疫 抑制,会导致 CAR-T 细胞线粒体功能障碍、衰竭和随后的 CAR-T 细胞耗竭,进而导致 CAR-T 细胞疗法的失败。 阐明抑制实 体瘤中 CAR-T 细胞功能的细胞内在和外在因素将促进免疫治疗的发展,从而在患者体内建立更持久有效的反应。 本文简要 介绍了肿瘤代谢相关的免疫抑制因素在 CAR-T 细胞疗法中的应用,并且介绍了在体内外提高 CAR-T 细胞代谢适应性和抗 肿瘤活性的最新进展和策略。

CAR-T cell therapy is a cutting-edge effective and rapidly evolving adoptive cell immunotherapy that recognizes tumor cell surface antigens independently of major histocompatibility complexes thereby reducing immune escape due to loss of tumor cell MHC-associated antigen presentation. Although it has been applied in blood cancer and made remarkable achievements its application in solid tumors is still affected by some adverse factors. Metabolism is one of the detrimental factors a set of basic cellular processes that not only sustain cell survival and proliferation but also serve as a means for cells to adapt to their local environment. Massive competition for nutrients such as carbohydrates and amino acids generated by tumor cell metabolism in the tumor microenvironment coupled with immunosuppression leads to mitochondrial dysfunction failure and subsequent CAR-T cell depletion leading to failure of CAR-T cell therapy. Elucidating cellular intrinsic and extrinsic factors that inhibit CAR-T cell function in solid tumors will facilitate the development of immunotherapy to establish a more durable and effective response in patients. In this review we briefly review the application of tumor metabolism-related immunosuppressive factors in CAR-T cell therapy as well as recent advances and strategies to improve the metabolic adaptability and antitumor activity of CAR-T cells in vivo and in vitro.