肿瘤细胞治疗研究
英文原题：Harnessing the tumor microenvironment to boost adoptive T cell therapy with engineered lymphocytes for solid tumors.
使用嵌合抗原受体（CAR）和T细胞受体（TCR）工程化T细胞的过继细胞疗法（ACT）代表了一种治疗血液系统恶性肿瘤的创新性治疗手段，但其在实体瘤中的应用仍不理想。
过继细胞疗法（ACT）使用嵌合抗原受体（CAR）和 T 细胞受体（TCR）工程化 T 细胞，是治疗血液系统恶性肿瘤的一种创新性治疗手段，但其在实体瘤中的应用仍不理想。肿瘤微环境（TME）为实现满意的治疗效果带来了若干需要克服的挑战，例如物理屏障（纤维化包膜和基质），以及阻碍 T 细胞功能的抑制性信号。其中一些障碍可通过将 ACT 与化疗/放疗、检查点抑制剂等其他抗肿瘤方法联合应用来应对。另一方面，前沿技术工具为克服 TME 固有特征、并在某些情况下利用这些特征来提升 ACT 疗效提供了机会。这些包括：利用趋化因子梯度和整合素表达以实现 T 细胞的优先归巢和外渗；通过增加抗原提呈和重塑 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改变；在 TCR-T 和 CAR-T 细胞上引入额外的合成受体，以提高 T 细胞的存活和适应能力。
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.
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