NLR、PLR、LMR及血清D-二聚体在肺癌免疫治疗疗效预测中的作用研究进展

The Progress of Research on the Roles of NLR, PLR, LMR, and Serum D-Dimer in Predicting the Efficacy of Immunotherapy for Lung Cancer

摘要: 肺癌的治疗手段主要包括手术、化疗、放疗、靶向治疗以及免疫治疗，随着精准治疗理念的提出，免疫治疗在肺癌各个治疗线中均扮演着重要角色，重塑了肺癌治疗格局，实现了多种单药和联合治疗的多种用药模式。免疫治疗通过激活人体自身免疫系统来对抗肿瘤，具有良好的安全性及耐受性，已迅速成为现代肿瘤学的主要治疗手段之一，以免疫检查点抑制剂(ICIs)为主的免疫治疗显著改善了非小细胞肺癌(NSCLC)患者的生存期，然而，仅有少数患者对单一疗法或联合疗法有反应，并且部分患者获得了持久疗效的同时，也承受免疫治疗带来的不良反应，免疫检查点抑制剂相关不良反应的发生率为54%~76%，尽管这些不良反应通常是轻微且可逆的，但严重者甚至导致患者死亡，例如免疫相关肺炎和免疫相关肝炎，因此需及时治疗，有些患者在治疗开始后数月才显现出生存获益，部分患者甚至不能从免疫治疗中获益，因此，迫切需要寻找到灵敏、高效的生物标志物，早期识别并预测患者使用免疫治疗的疗效，避免不良反应的发生。目前运用最广泛的生物标志物是PD-L1，但在晚期NSCLC中，不同的免疫治疗药物对于PD-L1表达水平甚至判读标准存在差异，且检测手段相对复杂及费用较高，其次，完善该检查涉及组织可及性，临床上完善PD-L1检测的总体比例较低，且既往有研究表明，PD-L1阴性表达的部分患者可从免疫治疗中获益，而部分高表达患者不能从中获益，这可能与肿瘤组织中PD-L1表达存在时空异质性有关，目前不能算作是完美的生物标志物，尤其对于复治患者，迫切需要更简便、快捷的检测手段，帮助临床医生识别出优势人群，为患者制定个体化治疗方案。目前，关于血液学生物标志物的相关研究越来越多，在本篇综述中，旨在总结有关免疫检查点抑制剂疗效的预测和预后生物标志物的相关知识，更好地服务于疾病。

Abstract: The treatment of lung cancer mainly includes surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. With the concept of precision treatment, immunotherapy plays an important role in various treatment regimens for lung cancer, reshaping the landscape of lung cancer treatment and achieving various single and combination therapy patterns. Immunotherapy activates the body’s immune system to fight against tumors, and has good safety and tolerability. It has rapidly become one of the main treatment modalities in modern oncology. Immunotherapy, mainly immune checkpoint inhibitors (ICIs), has significantly improved the survival of non-small cell lung cancer (NSCLC) patients. However, only a few patients respond to monotherapy or combination therapy, and some patients experience prolonged beneficial effects while also enduring adverse reactions brought on by immunotherapy. The incidence of adverse reactions related to immune checkpoint inhibitors is 54% to 76%. Although these adverse reactions are usually mild and reversible, severe cases can even lead to patient death, such as immune-related pneumonitis and immune-related hepatitis. Therefore, timely treatment is necessary. Some patients only show survival benefits from treatment after several months, while some cannot benefit at all from immunotherapy. Hence, there is an urgent need to identify sensitive and efficient biomarkers to early recognize and predict the efficacy of immunotherapy and avoid the occurrence of adverse reactions. Currently, the most widely used biomarker is PD-L1, but in advanced NSCLC, different immunotherapeutic drugs have differences in the level of PD-L1 expression and even interpretation criteria. Moreover, the detection methods are relatively complex and costly. Furthermore, the availability of the tissue involved in the perfect examination is relatively low clinically. Prior studies have shown that some PD-L1-negative patients can benefit from immunotherapy while some high-expressing patients cannot. This may be related to the spatiotemporal heterogeneity of PD-L1 expression in tumor tissue, making it not a perfect biomarker. Especially for recurrent patients, a simpler, more rapid detection method is urgently needed to help clinical doctors identify the favorable population and develop individualized treatment plans for patients. Currently, there is an increasing amount of research on hematological biomarkers. This review aims to summarize the knowledge related to predictive and prognostic biomarkers of immune checkpoint inhibitor efficacy, providing better service for the disease.