Immune checkpoint inhibition is a major component in today’s cancer immunotherapy. In recent years, the FDA has approved a number of immune checkpoint inhibitors (ICIs) for the treatment of melanoma, non-small-cell lung, breast and gastrointestinal cancers. These inhibitors, which target cytotoxic T-lymphocyte antigen-4, programmed cell death (PD-1), and programmed cell death ligand (PD-L1) checkpoints have assumed a leading role in immunotherapy. The same inhibitors exert significant antitumor effects by overcoming tumor cell immune evasion and reversing T-cell exhaustion. The initial impact of this therapy in cancer treatment was justly described as revolutionary, however, clinical as well as research data which followed demonstrated that these innovative drugs are costly, are associated with potentially severe adverse effects, and only benefit a small subset of patients. These limitations encouraged enhanced research and clinical efforts to identify predictive biomarkers to stratify patients who are most likely to benefit from this form of therapy. The discovery and characterization of this class of biomarkers is pivotal in guiding individualized treatment against various forms of cancer. Currently, there are three FDA-approved predictive biomarkers, however, none of which on its own can deliver a reliable and precise response to immune therapy. Present literature identifies the absence of precise predictive biomarkers and poor understanding of the mechanisms behind tumor resistance as the main obstacles facing ICIs immunotherapy. In the present text, we discuss the dual role of PD-L1 as a biomarker for response to immunotherapy and as an immune checkpoint. The contribution of mass spectrometry-based analysis, particularly the impact of protein post-translational modifications on the performance of this protein is underlined.
免疫检查点抑制是当今癌症免疫治疗的重要组成部分。近年来，美国食品药品监督管理局已批准多种免疫检查点抑制剂用于治疗黑色素瘤、非小细胞肺癌、乳腺癌及胃肠道癌症。这些靶向细胞毒性T淋巴细胞抗原-4、程序性细胞死亡蛋白-1及其配体的抑制剂已在免疫治疗中占据主导地位。通过克服肿瘤细胞免疫逃逸并逆转T细胞耗竭，此类抑制剂展现出显著的抗肿瘤效应。该疗法在癌症治疗中的初始影响被恰如其分地描述为革命性突破，然而后续临床与研究数据表明，这些创新药物成本高昂，可能引发严重不良反应，且仅能使少数患者获益。这些局限性促使学界加强研究并推进临床实践，以寻找能够筛选最可能从此类疗法中获益患者的预测性生物标志物。此类生物标志物的发现与表征对于指导个体化癌症治疗具有关键意义。目前已有三种经FDA批准的预测性生物标志物，但单独使用任何一种均无法对免疫治疗产生可靠且精准的疗效预测。现有文献指出，精准预测生物标志物的缺失以及对肿瘤耐药机制认知不足，是当前免疫检查点抑制剂治疗面临的主要障碍。本文重点探讨程序性细胞死亡配体-1作为免疫治疗应答生物标志物与免疫检查点的双重作用，并着重分析基于质谱的检测技术——特别是蛋白质翻译后修饰对该蛋白功能的影响。
肿瘤(癌症)患者之家