过继性T细胞治疗在非小细胞肺癌中的研究进展

T细胞是获得性抗肿瘤免疫的重要细胞亚群，但肿瘤组织中的T细胞数量少，且处于免疫抑制甚至耗竭状态，这是导致肿瘤免疫逃逸和免疫检查点抑制剂等抗肿瘤免疫治疗效果不佳的重要原因。过继性T细胞治疗主要包括肿瘤浸润淋巴细胞（tumor-infiltrating lymphocytes，TILs）、嵌合抗原受体T细胞（chimeric antigen receptor T-cell，CAR-T）、T细胞受体工程化T细胞（T-cell receptor engineering T cell，TCR-T）治疗，其通过体外筛选扩增富集肿瘤特异性T细胞或通过基因改造赋予T细胞新的抗原特异性（CAR-T、TCR-T），有效克服了肿瘤浸润T细胞不足的缺陷。虽然过继性T细胞治疗在非小细胞肺癌（non-small cell lung cancer，NSCLC）中的研究起步较晚，但已显示治疗的安全可行性和初步抗肿瘤效果，值得进一步深入研究。本文将对TILs、CAR-T、TCR-T的原理、培养方法、生物学特征以及在NSCLC治疗中的研究进展进行综述，以期为优化临床研究设计和开展新型NSCLC免疫治疗提供新思路。 

Research progress of adoptive T-cell therapy for non-small cell lung cancer

T cells play a vital role in adaptive anti-tumor immunity. However, infiltration of T cells into tumor tissues is limited. Even when infiltration occurs, the T cell activity is inhibited or even exhausted. The lack of activation of these T cells contributes to tumor immune escape and results in poor efficiency of anti-tumor immunotherapy, such as checkpoint inhibitors. Tumor-infiltrating lymphocytes (TILs), chimeric antigen receptor T-cell (CAR-T), and T-cell receptor engineering T cell (TCR-T) are the three main types of adoptive T-cell therapy strategies. In preparing adoptive T cells, tumor-reactive T cells are selected, amplified, and enriched for TILs, or tumor-specificity is modified using gene engineering methods for CAR-T and TCR-T. These adoptive T cells could overcome the deficiencies associated with tumor infiltrating T cells. Although the study of adoptive T-cell therapy has been relatively late in non-small cell lung cancer (NSCLC), preliminary results from clinical trials suggest a potential anti-tumor effect, which warrants further study. In this review, we summarize the principles, culture methods, and biological characteristics of adoptive T-cell therapy. We also describe the latest progress in the treatment of NSCLC. The aim is to provide new ideas for clinical research design and immunotherapy in NSCLC.