Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable responses in patients with certain haematological malignancies. However, its efficacy in solid tumors still remains disappointing. There are many factors that can potentially limit the effect of CAR T cell therapy in solid tumors. The infiltration, survival and persistence of CAR-T cells have faced numerous challenges for solid tumors. Vasculature and stromal barriers, hypoxia and high metabolism of solid tumors, immunosuppression of tumor microenvironment, as well as high heterogeneous tumor cells all are closely related to cancer progression and immune escape. These factors usually contribute to form an environment where tumor cells have an advantage over CAR T cells for their survival. Therefore, it is necessary to improve immune function of CAR T cells in solid tumor by developing strategies of reconstruct the environment or modifying CAR T cells. In this review, we outline the major obstacles of CAR-T cell therapy in solid tumors. And some rational strategies are also proposed to overcome the above challenges and barriers to CAR T anti-tumor efficacy.

中文翻译：

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实体瘤中嵌合抗原受体-T 细胞疗法的当前挑战和策略

嵌合抗原受体 (CAR) T 细胞疗法在某些血液系统恶性肿瘤患者中表现出显着反应。然而，其在实体瘤中的疗效仍然令人失望。有许多因素可能会限制 CAR T 细胞疗法在实体瘤中的效果。CAR-T 细胞的浸润、存活和持久性在实体瘤中面临着诸多挑战。血管和基质屏障、实体瘤的缺氧和高代谢、肿瘤微环境的免疫抑制以及高异质性肿瘤细胞都与癌症进展和免疫逃逸密切相关。这些因素通常有助于形成肿瘤细胞在生存方面优于 CAR T 细胞的环境。所以，有必要通过开发重建环境或修饰CAR T细胞的策略来提高实体瘤中CAR T细胞的免疫功能。在这篇综述中，我们概述了实体瘤中 CAR-T 细胞治疗的主要障碍。并且还提出了一些合理的策略来克服上述挑战和CAR T抗肿瘤功效的障碍。