Strati Areti, Adamopoulos Christos, Kotsantis Ioannis, Psyrri Amanda, Lianidou Evi, Papavassiliou Athanasios G
Analysis of Circulating Tumor Cells, Lab of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece.
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Int J Mol Sci. 2025 Jan 31;26(3):1235. doi: 10.3390/ijms26031235.
The PD1/PD-L1 axis plays an important immunosuppressive role during the T-cell-mediated immune response, which is essential for the physiological homeostasis of the immune system. The biology of the immunological microenvironment is extremely complex and crucial for the development of treatment strategies for immunotherapy. Characterization of the immunological, genomic or transcriptomic landscape of cancer patients could allow discrimination between responders and non-responders to anti-PD-1/PD-L1 therapy. Immune checkpoint inhibitor (ICI) therapy has shown remarkable efficacy in a variety of malignancies in landmark trials and has fundamentally changed cancer therapy. Current research focuses on strategies to maximize patient selection for therapy, clarify mechanisms of resistance, improve existing biomarkers, including PD-L1 expression and tumor mutational burden (TMB), and discover new biomarkers. In this review, we focus on the function of the PD-1/PD-L1 signaling pathway and discuss the immunological, genomic, epigenetic and transcriptomic landscape in cancer patients receiving anti-PD-1/PD-L1 therapy. Finally, we provide an overview of the clinical trials testing the efficacy of antibodies against PD-1/PD-L1.
PD1/PD-L1轴在T细胞介导的免疫反应中发挥重要的免疫抑制作用，这对免疫系统的生理稳态至关重要。免疫微环境的生物学特性极其复杂，对免疫治疗策略的制定至关重要。对癌症患者的免疫、基因组或转录组特征进行表征，有助于区分抗PD-1/PD-L1治疗的应答者和无应答者。免疫检查点抑制剂（ICI）疗法在具有里程碑意义的试验中已在多种恶性肿瘤中显示出显著疗效，并从根本上改变了癌症治疗方式。当前的研究重点在于优化患者治疗选择策略、阐明耐药机制、改进现有生物标志物（包括PD-L1表达和肿瘤突变负荷（TMB））以及发现新的生物标志物。在本综述中，我们重点关注PD-1/PD-L1信号通路的功能，并讨论接受抗PD-1/PD-L1治疗的癌症患者的免疫、基因组、表观遗传和转录组特征。最后，我们概述了测试抗PD-1/PD-L1抗体疗效的临床试验。
