Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
J Hematol Oncol. 2024 Jul 27;17(1):54. doi: 10.1186/s13045-024-01581-2.
Cancer immunotherapies, represented by immune checkpoint inhibitors (ICIs), have reshaped the treatment paradigm for both advanced non-small cell lung cancer and small cell lung cancer. Programmed death receptor-1/programmed death receptor ligand-1 (PD-1/PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) are some of the most common and promising targets in ICIs. Compared to ICI monotherapy, which occasionally demonstrates treatment resistance and limited efficacy, the dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 operates at different stages of T cell activation with synergistically enhancing immune responses against cancer cells. This emerging dual therapy heralds a new direction for cancer immunotherapy, which, however, may increase the risk of drug-related adverse reactions while improving efficacy. Previous clinical trials have explored combination therapy strategy of anti-PD-1/PD-L1 and anti-CTLA-4 agents in lung cancer, yet its efficacy remains to be unclear with the inevitable incidence of immune-related adverse events. The recent advent of bispecific antibodies has made this sort of dual targeting more feasible, aiming to alleviate toxicity without compromising efficacy. Thus, this review highlights the role of dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in treating lung cancer, and further elucidates its pre-clinical mechanisms and current advancements in clinical trials. Besides, we also provide novel insights into the potential combinations of dual blockade therapies with other strategies to optimize the future treatment mode for lung cancer.
癌症免疫疗法,以免疫检查点抑制剂(ICIs)为代表,已经改变了晚期非小细胞肺癌和小细胞肺癌的治疗模式。程序性死亡受体 1/程序性死亡受体配体 1(PD-1/PD-L1)和细胞毒性 T 淋巴细胞相关抗原 4(CTLA-4)是 ICI 中最常见和最有前途的靶点之一。与偶尔表现出治疗抵抗和疗效有限的 ICI 单药治疗相比,针对 PD-1/PD-L1 和 CTLA-4 的双重阻断免疫疗法在 T 细胞激活的不同阶段起作用,协同增强对癌细胞的免疫反应。这种新兴的双重疗法为癌症免疫疗法开辟了新的方向,但在提高疗效的同时,也可能增加与药物相关的不良反应风险。以前的临床试验已经探讨了抗 PD-1/PD-L1 和抗 CTLA-4 药物在肺癌中的联合治疗策略,但由于免疫相关不良反应的不可避免发生,其疗效仍不清楚。最近双特异性抗体的出现使得这种双重靶向治疗更加可行,旨在减轻毒性而不影响疗效。因此,本综述强调了针对 PD-1/PD-L1 和 CTLA-4 的双重阻断免疫疗法在治疗肺癌中的作用,并进一步阐明了其在临床前机制和临床试验中的最新进展。此外,我们还为双重阻断疗法与其他策略的潜在联合提供了新的见解,以优化肺癌的未来治疗模式。
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