使用嵌合抗原受体 (CAR) 和 T 细胞受体 (TCR) 改造的 T 细胞的过继细胞疗法 (ACT) 代表了治疗血液恶性肿瘤的创新治疗方法，但其在实体瘤中的应用仍然不够理想。肿瘤微环境 (TME) 为获得令人满意的治疗效果提出了一些需要克服的挑战，例如物理屏障（纤维化包膜和基质）和阻碍 T 细胞功能的抑制信号。通过将 ACT 与其他抗肿瘤方法（例如化疗/放疗和检查点抑制剂）相结合，可以克服其中一些障碍。另一方面，尖端技术工具提供了克服并在某些情况下利用 TME 内在特征来提高 ACT 功效的机会。其中包括：利用趋化因子梯度和整合素表达来优先 T 细胞归巢和外渗；通过增加抗原呈递和重塑 T 细胞表型，对 TCR-T 和 CAR-T 细胞产生直接或间接影响的代谢变化；在 TCR-T 和 CAR-T 细胞上引入额外的合成受体，旨在提高 T 细胞的存活率和适应性。© 2024。作者获得 Springer-Verlag GmbH 德国（Springer Nature 旗下公司）的独家许可。

Adoptive cell therapy (ACT) using Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR) engineered T cells represents an innovative therapeutic approach for the treatment of hematological malignancies, yet its application for solid tumors is still suboptimal. The tumor microenvironment (TME) places several challenges to overcome for a satisfactory therapeutic effect, such as physical barriers (fibrotic capsule and stroma), and inhibitory signals impeding T cell function. Some of these obstacles can be faced by combining ACT with other anti-tumor approaches, such as chemo/radiotherapy and checkpoint inhibitors. On the other hand, cutting edge technological tools offer the opportunity to overcome and, in some cases, take advantage of TME intrinsic characteristics to boost ACT efficacy. These include: the exploitation of chemokine gradients and integrin expression for preferential T-cell homing and extravasation; metabolic changes that have direct or indirect effects on TCR-T and CAR-T cells by increasing antigen presentation and reshaping T cell phenotype; introduction of additional synthetic receptors on TCR-T and CAR-T cells with the aim of increasing T cells survival and fitness.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.