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Abstract：
T cells are critical to fight pathogenic microbes and combat malignantly transformed cells in the fight against cancer. To exert their effector function, T cells produce effector molecules, such as the pro-inflammatory cytokines IFN-γ, TNF-α and IL-2. Tumors possess many inhibitory mechanisms that dampen T cell effector function, limiting the secretion of cytotoxic molecules. As a result, the control and elimination of tumors is impaired. Through recent advances in genomic editing, T cells can now be successfully modified via CRISPR/Cas9 technology. For instance, engaging (post-)transcriptional mechanisms to enhance T cell cytokine production, the retargeting of T cell antigen specificity or rendering T cells refractive to inhibitory receptor signaling can augment T cell effector function. Therefore, CRISPR/Cas9-mediated genome editing might provide novel strategies for cancer immunotherapy. Recently, the first-in-patient clinical trial was successfully performed with CRISPR/Cas9-modified human T cell therapy. In this review, a brief overview of currently available techniques is provided, and recent advances in T cell genomic engineering for the enhancement of T cell effector function for therapeutic purposes are discussed.
摘要：
T细胞对于对抗病原微生物和对抗癌症中的恶性转化细胞至关重要。为了发挥它们的效应子功能，T细胞产生效应分子，如促炎细胞因子IFN-γ，TNF-α和IL-2。肿瘤具有许多抑制T细胞效应子功能的抑制机制，限制细胞毒性分子的分泌。因此,肿瘤的控制和消除受损。通过基因组编辑的最新进展，现在可以通过CRISPR/Cas9技术成功修饰T细胞。例如,参与（后）转录机制以增强T细胞细胞因子的产生，T细胞抗原特异性的重新靶向或使T细胞对抑制性受体信号传导具有折射作用可以增强T细胞效应子功能。因此,CRISPR/Cas9介导的基因组编辑可能为癌症免疫治疗提供新策略。最近,首次患者临床试验通过CRISPR/Cas9修饰的人T细胞疗法成功进行.在这次审查中,提供了当前可用技术的简要概述，讨论了用于治疗目的的增强T细胞效应子功能的T细胞基因组工程的最新进展。
