Piao Mingjian, Zhang Nan, Li Jiongyuan, Li Chengjie, Xun Ziyu, Zhang Longhao, Wang Shanshan, Sun Boyu, Li Shuofeng, Yang Xu, Yang Xiaobo, Wang Hanping, Zhao Haitao
Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, China.
Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, China.
Int Immunopharmacol. 2025 Feb 6;147:114052. doi: 10.1016/j.intimp.2025.114052. Epub 2025 Jan 11.
A shift toward a T cell exhaustion phenotype is associated with the upregulation of expression of programmed cell death protein 1 (PD-1) on T lymphocytes in patients with malignant solid tumors. The interaction between PD-1 and programmed death-ligand 1 (PD-L1) inhibits PD-1 T lymphocyte function, impacting their anti-tumor immune activity. Immune checkpoint inhibitors targeting PD-1/PD-L1 have revolutionized the treatment of various solid malignancies, improving therapeutic efficacy and survival outcomes. Peripheral blood analysis of liquid biopsies is being increasingly used to identify populations most likely to benefit from various treatment modalities. PD-1 T lymphocytes represent the primary cell population responsive to immunotherapeutic interventions for patients with solid malignancies, as evidenced by the altered PD-1 expression levels and proportion of cells comprising the overall population of immunocytes. PD-1 T cells in peripheral blood exert an associative and reciprocal predictive effect on homologous intratumoral cells. Distinct subpopulations of PD-1 T cells exhibit differential ability to proliferate in the periphery and can be characterized by tumor antigen-specific and exhaustion phenotypes. These characteristics have prognostic implications, aiding in the prediction of the efficacy of antitumor therapy and predicting survival outcomes. We highlight distinct subpopulations of PD-1 T cells, their exhaustion and antigen-specific phenotypes, and their dynamic changes over treatment, providing insights into their utility for tailoring personalized therapies. For the first time, this review discusses the role of peripheral PD-1 T lymphocytes as prognostic biomarkers in liquid biopsies, focusing on their clinical significance, predictive value during therapy, and future research directions.
在恶性实体瘤患者中，T细胞耗竭表型的转变与T淋巴细胞上程序性细胞死亡蛋白1（PD-1）表达的上调有关。PD-1与程序性死亡配体1（PD-L1）之间的相互作用抑制了PD-1 T淋巴细胞的功能，影响其抗肿瘤免疫活性。靶向PD-1/PD-L1的免疫检查点抑制剂彻底改变了各种实体恶性肿瘤的治疗方式，提高了治疗效果和生存结局。液体活检的外周血分析越来越多地用于确定最有可能从各种治疗方式中获益的人群。PD-1 T淋巴细胞是实体恶性肿瘤患者对免疫治疗干预有反应的主要细胞群体，这一点从免疫细胞总体中PD-1表达水平和细胞比例的改变可以得到证明。外周血中的PD-1 T细胞对同源肿瘤内细胞具有关联和相互的预测作用。PD-1 T细胞的不同亚群在外周具有不同的增殖能力，并且可以通过肿瘤抗原特异性和耗竭表型来表征。这些特征具有预后意义，有助于预测抗肿瘤治疗的疗效和生存结局。我们重点介绍了PD-1 T细胞的不同亚群、它们的耗竭和抗原特异性表型，以及它们在治疗过程中的动态变化，为其在定制个性化治疗中的应用提供了见解。本综述首次讨论了外周PD-1 T淋巴细胞作为液体活检中预后生物标志物的作用，重点关注其临床意义、治疗期间的预测价值以及未来的研究方向。
