Lycan Thomas W, Norton Dustin L, Ohar Jill A
Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Int J Chron Obstruct Pulmon Dis. 2024 Dec 9;19:2689-2703. doi: 10.2147/COPD.S490252. eCollection 2024.
Immune checkpoint inhibitors are a standard treatment option for many patients with cancer and are most frequently used to treat lung cancer. Chronic obstructive pulmonary disease (COPD) is the most common comorbidity of patients with lung cancer. As the cancer-specific survival of patients with lung cancer continues to increase with modern treatments, it is critical to optimize comorbidities to improve overall survival. This literature review aimed to summarize current research on the impact of COPD upon immunotherapy outcomes.
A comprehensive search was conducted in the PubMed database using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria focused on peer-reviewed articles published between 2010 and 2024 that addressed COPD, cancer, and immune checkpoint inhibitors. The study team screened the studies for relevance and then synthesized them narratively.
This review identified 37 studies that met the inclusion criteria. Findings suggest that COPD is predictive of improved efficacy but slightly worse toxicity from immune checkpoint inhibitor therapy. The chronic inflammation of COPD leads to immune exhaustion including the overexpression of immune checkpoints on T-cells. Particularly within "hot" tumors that have higher concentrations of tumor-infiltrating lymphocytes, the COPD-related increase in programmed cell death protein 1 (PD-1) signaling likely creates sensitivity to immune checkpoint inhibitors. However, COPD can also lead to respiratory dysfunction, debility, and interstitial lung disease; each of which increases the severity of immune-related adverse events.
COPD is a critical comorbidity that has a significant impact on many patients with cancer who receive treatment with immune checkpoint inhibitors. Future research is needed to design interventions to optimize COPD care in this high-risk patient population.
免疫检查点抑制剂是许多癌症患者的标准治疗选择，最常用于治疗肺癌。慢性阻塞性肺疾病（COPD）是肺癌患者最常见的合并症。随着现代治疗方法使肺癌患者的癌症特异性生存率不断提高，优化合并症以提高总生存率至关重要。这篇文献综述旨在总结当前关于COPD对免疫治疗结果影响的研究。
使用系统评价和Meta分析的首选报告项目（PRISMA）指南在PubMed数据库中进行了全面检索。纳入标准集中在2010年至2024年期间发表的、涉及COPD、癌症和免疫检查点抑制剂的同行评审文章。研究团队筛选了相关研究，然后进行叙述性综合分析。
本综述确定了37项符合纳入标准的研究。研究结果表明，COPD预示着免疫检查点抑制剂治疗的疗效改善，但毒性略差。COPD的慢性炎症导致免疫耗竭，包括T细胞上免疫检查点的过度表达。特别是在肿瘤浸润淋巴细胞浓度较高的“热”肿瘤中，COPD相关的程序性细胞死亡蛋白1（PD-1）信号增加可能使肿瘤对免疫检查点抑制剂产生敏感性。然而，COPD也可导致呼吸功能障碍、虚弱和间质性肺疾病；每一种情况都会增加免疫相关不良事件的严重程度。
COPD是一种关键的合并症，对许多接受免疫检查点抑制剂治疗的癌症患者有重大影响。未来需要开展研究，设计干预措施以优化这一高风险患者群体的COPD护理。
