[摘要] T 细胞受体工程化T 细胞（T cell receptor-engineered T cells, TCR-T）是目前肿瘤免疫治疗领域的研究热点之一，从2006 年首个临床试验成功至今已经取得了一系列令人鼓舞的成果，但快速发展的同时其在杀伤性、安全性、持久性这三方面仍面临着许多问题。改善肿瘤免疫微环境，增强TCR-T的趋化、浸润与活化将是提高其杀伤肿瘤作用的关键；新抗原具有高度的肿瘤特异性与免疫原性，是保障治疗安全有效和实现个体化肿瘤免疫治疗的基础；另外，回输低分化的T细胞亚群是产生持久免疫应答的可靠方法。本文将结合当前的研究进展，从以上三个角度阐述TCR-T抗肿瘤治疗的现状与挑战。

[Abstract] T cell receptor-engineered T cell (TCR-T) therapy is one of the hotspots in the field of cancer immunotherapy. Considerable achievements have been made since the first successful clinical trial in 2006. However, problems still remain in cytotoxicity, safety and persistence of TCR-T therapy despite the rapid development. Improving the immunosuppressive tumor microenvironment and enhancingchemotaxis,infiltration as well as activation of TCR-T cell will be the key to improve its anti-tumor effect. Neoantigens, which are highly tumor-specific and immunogenic,are the basis for safe and effective treatment and individualized cancer immunotherapy. Besides,infusion of less differentiated T cell subsets is also a reliable way to generate a long-lasting immune response. Here, combing with current research progress, we offer our perspectives on the current situation and challenges of TCR-T from the three aspects above.

国家自然科学基金资助项目（No.81672367)