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表皮生长因子受体(EGFR)突变型肺癌的免疫治疗策略

Immunotherapy strategy of EGFR mutant lung cancer.

作者信息

Yu Shaorong, Liu Delin, Shen Bo, Shi Meiqi, Feng Jifeng

机构信息

Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University Jiangsu, China.

出版信息

Am J Cancer Res. 2018 Oct 1;8(10):2106-2115. eCollection 2018.

Abstract

EGFR-mutant lung cancer is an important molecular subtype in Asia considering that almost 40%-50% of patients with lung adenocarcinoma in Asian carry the active EGFR mutaiton. People have greatly anticipated the efficacy of PD-1/PD-L1 monoclonal antibody in lung cancer treatment but anti-PD-1/PD-L1 treatment failed to positively affect these patients. The NCCN guidelines do not recommend immunotherapy to patients with NSCLC carrying EGFR mutation at present. However, the reason why EGFR-mutant lung cancer patients show poor response to anti-PD-1/PD-L1 treatment is still unknown. Immune suppression and tolerance are the main characteristics of tumor. The PD-1/PD-L1 co-inhibitory molecule is probably not the main escape route of this tumor type. The main characteristic of EGFR-mutant lung cancer is the activation of the EGFR signaling pathway. EGFR activation is likely responsible for the uninflamed tumor microenvironment of this type tumor and particiaptes in immunosuppression and immune escape. Accumulating evidence proved that activation of EGFR signaling pathway is essential to the generation of Treg and tolerogenic DCs. In this review, we summarize the efficacy of PD-1/PD-L1 monoclonal antibiodies in patients with EGFR-mutant lung cancer patients; provide evidence to analyze the potential reason why these patients cannot benefit from anti-PD-1/PD-L1 treatment, and explore the strategy that shoud be adopted in the future.

摘要

考虑到亚洲近40%-50%的肺腺癌患者携带活性表皮生长因子受体(EGFR)突变,EGFR突变型肺癌是亚洲一种重要的分子亚型。人们对程序性死亡受体1(PD-1)/程序性死亡配体1(PD-L1)单克隆抗体在肺癌治疗中的疗效寄予厚望,但抗PD-1/PD-L1治疗未能对这些患者产生积极影响。目前,美国国立综合癌症网络(NCCN)指南不建议对携带EGFR突变的非小细胞肺癌(NSCLC)患者进行免疫治疗。然而,EGFR突变型肺癌患者对抗PD-1/PD-L1治疗反应不佳的原因仍不清楚。免疫抑制和免疫耐受是肿瘤的主要特征。PD-1/PD-L1共抑制分子可能不是这类肿瘤的主要逃逸途径。EGFR突变型肺癌的主要特征是EGFR信号通路的激活。EGFR激活可能是这类肿瘤无炎症肿瘤微环境的原因,并参与免疫抑制和免疫逃逸。越来越多的证据证明,EGFR信号通路的激活对调节性T细胞(Treg)和耐受性树突状细胞(DCs)的产生至关重要。在这篇综述中,我们总结了PD-1/PD-L1单克隆抗体在EGFR突变型肺癌患者中的疗效;提供证据分析这些患者不能从抗PD-1/PD-L1治疗中获益的潜在原因,并探索未来应采取的策略。

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