Abaza Abdelrahman, Sid Idris Faten, Anis Shaikh Humna, Vahora Ilma, Moparthi Kiran Prasad, Al Rushaidi Majdah T, Muddam Meghana Reddy, Obajeun Omobolanle A, Jaramillo Arturo P, Khan Safeera
Pathology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Pediatrics, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Cureus. 2023 Sep 2;15(9):e44582. doi: 10.7759/cureus.44582. eCollection 2023 Sep.
The advent of immune checkpoint inhibitors has revolutionized cancer therapy by leveraging the body's immune system to combat malignancies effectively. Among these groundbreaking agents, programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have emerged as pivotal therapeutic approaches. PD-L1, a key protein expressed on the surface of various cells, including cancer cells, plays a central role in immune regulation by interacting with the programmed cell death protein 1 (PD-1) receptor on T-cells leading to immune suppression. The substantial increase in PD-L1 expression on cancer cell surfaces has driven the exploration of PD-1/PD-L1 inhibitors as potential immunotherapeutic agents. These inhibitors are monoclonal antibodies designed to impede the PD-L1 and PD-1 interaction and disrupt the immunosuppressive signal, thereby reinvigorating the anti-tumor immune response mediated by activated T-cells. Clinical trials investigating PD-1/PD-L1 inhibitors have demonstrated remarkable efficacy in the treatment of diverse advanced or metastatic cancers, including leukemia, non-small cell lung (NSCLC), hepatocellular, melanoma, gastric, colorectal, and breast cancers, among others. Regulatory approvals have been granted for both monotherapy and combination therapy with other cancer treatments, encompassing chemotherapy and additional immune checkpoint inhibitors. While PD-1/PD-L1 inhibitors have exhibited significant success, they are not devoid of challenges. The emergence of intrinsic or acquired resistance, as well as immune-related adverse events, warrants thorough investigation and management. Consequently, researchers have embarked on combination trials to augment the therapeutic potential of PD-1/PD-L1 inhibitors and surmount resistance mechanisms.
免疫检查点抑制剂的出现彻底改变了癌症治疗方式，它通过利用人体免疫系统有效地对抗恶性肿瘤。在这些具有开创性的药物中，程序性细胞死亡蛋白1（PD-1）和程序性细胞死亡配体1（PD-L1）抑制剂已成为关键的治疗方法。PD-L1是一种在包括癌细胞在内的各种细胞表面表达的关键蛋白，它通过与T细胞上的程序性细胞死亡蛋白1（PD-1）受体相互作用，在免疫调节中发挥核心作用，导致免疫抑制。癌细胞表面PD-L1表达的大幅增加推动了对PD-1/PD-L1抑制剂作为潜在免疫治疗药物的探索。这些抑制剂是单克隆抗体，旨在阻碍PD-L1与PD-1的相互作用并破坏免疫抑制信号，从而恢复由活化T细胞介导的抗肿瘤免疫反应。研究PD-1/PD-L1抑制剂的临床试验已证明其在治疗多种晚期或转移性癌症方面具有显著疗效，包括白血病、非小细胞肺癌（NSCLC）、肝细胞癌、黑色素瘤、胃癌、结直肠癌和乳腺癌等。监管部门已批准其单药治疗以及与其他癌症治疗方法（包括化疗和其他免疫检查点抑制剂）的联合治疗。虽然PD-1/PD-L1抑制剂已取得显著成功，但它们并非没有挑战。内在或获得性耐药的出现以及免疫相关不良事件，都需要进行深入研究和管理。因此，研究人员已开展联合试验，以增强PD-1/PD-L1抑制剂的治疗潜力并克服耐药机制。
