Department of Internal Medicine, Lorestan University of Medical Sciences, Lorestan, Iran.
National Institute for Genetic Engineering and Biotechnology (NIGEB), P.O. Box: 14965/161, Tehran, Iran.
Pathol Res Pract. 2023 Jun;246:154470. doi: 10.1016/j.prp.2023.154470. Epub 2023 Apr 20.
The immune system uses various immune checkpoint axes to adjust responses, support homeostasis, and deter self-reactivity and autoimmunity. Nevertheless, non-small-cell lung carcinoma (NSCLC) can use protective mechanisms to facilitate immune evasion, which leads to potentiated cancer survival and proliferation. In this light, many blocking anti-bodies have been developed to negatively regulate checkpoint molecules, in particular, programmed cell death protein 1 (PD-1) / PD-ligand 1 (L1), and bypass these immune suppressive mechanisms. Meanwhile, anti-PD-1 anti-bodies such as nivolumab, pembrolizumab, cemiplimab, and sintilimab have shown excellent competence in successfully inspiring immune responses versus NSCLC. Accordingly, the United States Food and Drug Administration (FDA) has recently approved nivolumab (alone or in combination with ipilimumab) and pembrolizumab (alone or in combination with chemotherapy) as first-line treatment for advanced NSCLC patients. However, PD-1 blockade monotherapy remains inefficient in more than 60% of NSCLC patients, and many patients don't respond or acquire resistance to this modality. Also, toxicities related to anti-PD-1 anti-body have been progressively identified in clinical trials and oncology practice. Herein, we will outline the clinical benefits of PD-1 blockade therapy alone or in combination with other treatments (e.g., chemotherapy, radiotherapy, anti-angiogenic therapy) in NSCLC patients. Moreover, we will take a glimpse into the recently identified predictive biomarkers to determine patients most likely to suffer serious adverse events to decrease untoward toxicity risk and diminish treatment costs.
免疫系统利用各种免疫检查点轴来调节反应、支持内稳态，并防止自身反应和自身免疫。然而，非小细胞肺癌（NSCLC）可以利用保护机制来促进免疫逃逸，从而导致癌症的存活和增殖能力增强。有鉴于此，许多阻断抗体已被开发出来以负调控检查点分子，特别是程序性细胞死亡蛋白 1（PD-1）/PD-配体 1（L1），并绕过这些免疫抑制机制。与此同时，抗 PD-1 抗体，如nivolumab、pembrolizumab、cemiplimab 和 sintilimab，在成功激发针对 NSCLC 的免疫反应方面表现出了卓越的能力。因此，美国食品和药物管理局（FDA）最近批准 nivolumab（单独使用或与 ipilimumab 联合使用）和 pembrolizumab（单独使用或与化疗联合使用）作为晚期 NSCLC 患者的一线治疗药物。然而，PD-1 阻断单药治疗在超过 60%的 NSCLC 患者中仍然无效，而且许多患者对这种治疗方式没有反应或产生耐药性。此外，与抗 PD-1 抗体相关的毒性已在临床试验和肿瘤学实践中逐渐被识别。在此，我们将概述 PD-1 阻断治疗单独或与其他治疗方法（如化疗、放疗、抗血管生成治疗）联合在 NSCLC 患者中的临床获益。此外，我们还将探讨最近确定的预测生物标志物，以确定最有可能发生严重不良事件的患者，从而降低不良毒性风险并降低治疗成本。
