Department of Medical Oncology, Shouguang Hospital of Traditional Chinese Medicine, Shouguang, Shandong Province, People's Republic of China.
Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.
Expert Rev Mol Med. 2022 Apr 4;24:e16. doi: 10.1017/erm.2022.9.
Although immune checkpoint inhibitors (ICIs) have produced remarkable responses in non-small cell lung cancer (NSCLC) patients, receivers still have a relatively low response rate. Initial response assessment by conventional imaging and evaluation criteria is often unable to identify whether patients can achieve durable clinical benefit from ICIs. Overall, there are sparse effective biomarkers identified to screen NSCLC patients responding to this therapy. A lot of studies have reported that patients with specific gene mutations may benefit from or resist to immunotherapy. However, the single gene mutation may be not effective enough to predict the benefit from immunotherapy for patients. With the advancement in sequencing technology, further studies indicate that many mutations often co-occur and suggest a drastic transformation of tumour microenvironment phenotype. Moreover, co-mutation events have been reported to synergise to activate or suppress signalling pathways of anti-tumour immune response, which also indicates a potential target for combining intervention. Thus, the different mutation profile (especially co-mutation) of patients may be an important concern for predicting or promoting the efficacy of ICIs. However, there is a lack of comprehensive knowledge of this field until now. Therefore, in this study, we reviewed and elaborated the value of cancer mutation profile in predicting the efficacy of immunotherapy and analysed the underlying mechanisms, to provide an alternative way for screening dominant groups, and thereby, optimising individualised therapy for NSCLC patients.
尽管免疫检查点抑制剂(ICIs)在非小细胞肺癌(NSCLC)患者中产生了显著的反应,但接受者的反应率仍然相对较低。传统影像学和评估标准的初步反应评估通常无法确定患者是否能从 ICI 中获得持久的临床获益。总体而言,目前还没有有效的生物标志物来筛选对这种治疗有反应的 NSCLC 患者。许多研究报告称,具有特定基因突变的患者可能受益于或抵抗免疫治疗。然而,单一基因突变可能不足以预测患者从免疫治疗中获益。随着测序技术的进步,进一步的研究表明,许多突变经常同时发生,并提示肿瘤微环境表型发生剧烈转变。此外,共突变事件已被报道协同激活或抑制抗肿瘤免疫反应的信号通路,这也表明联合干预的潜在靶点。因此,患者的不同突变谱(尤其是共突变)可能是预测或促进 ICI 疗效的一个重要关注点。然而,到目前为止,人们对这一领域还缺乏全面的了解。因此,在本研究中,我们回顾并阐述了癌症突变谱在预测免疫治疗疗效中的价值,并分析了其潜在机制,为筛选优势群体提供了一种替代方法,从而优化 NSCLC 患者的个体化治疗。