近年来，以T淋巴细胞为主的免疫细胞疗法在血液系统肿瘤和部分实体瘤中取得了一定的进展。然而，其对大部分 实体瘤治疗的有效性和安全性仍面临着诸多挑战，如肿瘤抗原异质性和免疫逃逸、免疫细胞浸润能力差、免疫抑制微环境、代谢 微环境阻碍和T细胞耗竭等，这些问题限制了免疫细胞对实体瘤治疗的疗效进一步的提升。通过寻找新抗原、设计多靶点CAR、 过表达趋化因子受体及细胞因子、敲除抑制性信号分子、增强T细胞代谢能力、联合免疫检查点抑制剂，以及表观遗传修饰等手 段能够有效改善免疫细胞在实体瘤治疗中的效果。本文系统性地对TIL、TCR-T细胞和CAR-T细胞为代表的免疫细胞对实体瘤 治疗的研究现状、面临的挑战和解决策略进行评述。

In recent years, T-lymphocyte-based immune cell therapies have achieved remarkable progress in hematologic tumors and some solid tumors. However, there still remain many challenges in immune cell therapies for solid tumors, such as antigen heterogeneity, immune evasion, poor immune cell infiltration, immunosuppressive microenvironment, metabolic obstructive microenvironment and T cell exhaustion, limiting further improvement in immune cell therapies for solid tumors. The effectiveness of immune cells in solid tumor therapy can be efficiently improved by searching for new antigens, designing multi-target CARs, overexpressing chemokine receptors and cytokines, knocking down inhibitory signaling molecules, enhancing T cell metabolic capacity, combining immune checkpoint inhibitors and epigenetic modifications. This article reviews systematically the current status of research, challenges and solution strategies of immune cell therapies for solid tumors, such as tumor-infiltrating lymphocyte (TIL) therapy, TCR-T (T cell receptor-engineered T) cell therapy and CAR-T (chimeric antigen receptor T) cell therapy.

重大新药创制科技重大专项（No. 2020ZX09201-009）； 国家自然科学基金面上项目（No. 81771781）；国家自然科学基金青年 基金（No.82203548）；河南省重大公益专项（No. 201300310400）