肺癌免疫治疗耐药的临床现状与研究进展

Clinical status and research progress of immunotherapy resistance in lung cancer

肺癌是全球范围内发病率与致死率最高的恶性肿瘤。近年来,基于程序性细胞死亡蛋白-1(programmed death-1,PD-1)及其配体(programmed death-ligand 1,PD-L1)免疫检查点抑制剂为代表的新兴免疫治疗在肺癌领域中取得了革命性突破,适应证已从驱动基因阴性的晚期或局部晚期肺癌前移至围术期肺癌的辅助与新辅助治疗中,越来越多的PD-1、PD-L1单抗在肺癌领域中获批。然而,随着免疫治疗的广泛应用,耐药问题逐渐凸显,能够响应免疫治疗而获益的肺癌患者仅占少部分,给肺癌免疫治疗带来了新一轮的挑战。本文梳理了肺癌免疫治疗耐药的临床现状,并对其耐药机制和应对策略的前沿进展进行综述,旨在为临床医师拟定个体化、精准化的治疗方案提供思路和依据。

Lung cancer is the malignant tumor with the highest incidence and lethality globally.In recent years,emerging immunotherapy based on the immune checkpoint inhibitors,programmed cell death protein-1 and its ligand(PD-1/L1),as a representative,has made revolutionary breakthroughs in the field of lung cancer.The indications for this treatment mode have moved from driver-gene-negative advanced or locally advanced lung cancer to adjuvant and neoadjuvant treatment of perioperative lung cancer,and an increasing number of monoclonal antibodies against PD-1 and PD-L1 has been approved for the treatment of lung cancer.However,with the widespread use of immunotherapy,the problem of drug resistance has gradually come to the fore.Only a small proportion of the overall lung cancer population responds to immunotherapy,bringing a new round of challenges to lung cancer treatment.In this paper,the clinical status of immunotherapy resistance in lung caner is reviewed,and cutting-edge advances in knowledge of resistance mechanisms and coping strategies are reviewed,with the aim of providing clinicians with ideas and the basis for formulating individualized,precise treatment plans.