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非小细胞肺癌免疫治疗生物标志物研究进展

Research Progress of Biomarkers for Immunotherapy on Non-small Cell Lung Cancer

  • 摘要: 非小细胞肺癌约占所有肺癌类型的75%~80%,5年生存率仅为15%。近年来人们对肺癌精准治疗的认识明显提高,但非小细胞肺癌的治疗仍面临挑战,驱动基因阴性患者的治疗方式十分有限,晚期患者的预后仍较差。免疫治疗药物可以通过阻断免疫检查点使抗肿瘤T细胞免疫反应恢复或增强,或者T细胞受体转导的T细胞免疫疗法靶向大部分的肿瘤特异性抗原从而起到抗肿瘤作用。目前,仅免疫检查点治疗的临床试验表明,非小细胞肺癌中非选择性人群的客观缓解率为10%~20%,仍有大部分患者不能从免疫治疗中获益,故优势人群的筛选仍十分重要。PD-L1是目前最常用的免疫治疗的疗效预测标志物,但仍存在一定的局限性,不能作为常规标志物应用于临床。另有相关研究表明:肿瘤突变负荷、肿瘤浸润淋巴细胞、微卫星不稳定等都是预测免疫治疗疗效的重要生物标志物。本文将对目前临床研究中关于免疫治疗的相关生物标志物新进展作系统综述。

     

    Abstract: Non-small cell lung cancer accounts for 75%-80% of all lung cancers, and the 5-year survival rate is only 15%. Recently, people's awareness of the precision medicine project of lung cancer has been significantly improved, but the treatment of NSCLC and driver gene-negative patients is still facing challenge and limitation. The prognosis of patients with advanced stage is still poor. Immunotherapy plays an anti-tumor role by restoring or enhancing anti-tumor T cell immune response by blocking the immune checkpoint, or T cell receptor-mediated T cell immunotherapy targeting most of tumor specific antigens. However, only the clinical trials of checkpoint inhibitors show that the objective response rate of non-selective population is 10%-20%, most NSCLC patients can't benefit from immunotherapy, so the screening of the dominant population is still very important. At present, PD-L1 is the most commonly used prognostic marker, but it still has some limitations and can not be used as a routine marker in clinical practice. Other studies have shown that tumor mutation burden, tumor infiltrating lymphocytes and microsatellite instability are important biomarkers for predicting the efficacy of immunotherapy. In this paper, we will present a systematic review of biomarkers related to immunotherapy in current clinical studies.

     

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