The success of PD-1/PD-L1-targeted therapy in lung cancer has resulted in great enthusiasm for additional immunotherapies in development to elicit similar survival benefits, particularly in patients who do not respond to or are ineligible for PD-1 blockade. CD47 is an immunosuppressive molecule that binds SIRPα on antigen-presenting cells to regulate an innate immune checkpoint that blocks phagocytosis and subsequent activation of adaptive tumor immunity. In lung cancer, CD47 expression is associated with poor survival and tumors with EGFR mutations, which do not typically respond to PD-1 blockade. Given its prognostic relevance, its role in facilitating immune escape, and the number of agents currently in clinical development, CD47 blockade represents a promising next-generation immunotherapy for lung cancer. In this review, we briefly summarize how tumors disrupt the cancer immunity cycle to facilitate immune evasion and their exploitation of immune checkpoints like the CD47–SIRPα axis. We also discuss approved immune checkpoint inhibitors and strategies for targeting CD47 that are currently being investigated. Finally, we review the literature supporting CD47 as a promising immunotherapeutic target in lung cancer and offer our perspective on key obstacles that must be overcome to establish CD47 blockade as the next standard of care for lung cancer therapy.
PD-1/PD-L1靶向疗法在肺癌治疗中的成功，激发了人们对开发其他免疫疗法以取得类似生存获益的巨大热情，尤其针对那些对PD-1阻断无反应或不适宜接受该治疗的患者。CD47是一种免疫抑制分子，通过与抗原呈递细胞上的SIRPα结合，调控先天免疫检查点，从而阻断吞噬作用及后续适应性肿瘤免疫的激活。在肺癌中，CD47表达与不良预后及EGFR突变肿瘤相关，而这类肿瘤通常对PD-1阻断治疗不敏感。鉴于CD47的预后相关性、其在促进免疫逃逸中的作用以及目前处于临床开发阶段的多种靶向药物，CD47阻断疗法有望成为肺癌的下一代免疫治疗策略。本综述简要总结了肿瘤如何破坏癌症免疫循环以实现免疫逃逸，以及如何利用CD47–SIRPα轴等免疫检查点；同时讨论了已获批的免疫检查点抑制剂及当前正在研究的CD47靶向策略。最后，我们回顾了支持CD47作为肺癌潜在免疫治疗靶点的相关文献，并对确立CD47阻断疗法作为肺癌治疗新标准所需克服的关键障碍提出了见解。
CD47: The Next Frontier in Immune Checkpoint Blockade for Non-Small Cell Lung Cancer
肿瘤(癌症)患者之家