EGFR突变非小细胞肺癌患者围手术期免疫疗法：意外的潜在益处
Perioperative immunotherapy for patients with EGFR mutant non-small cell lung cancer: Unexpected potential benefits
影响因子:8.30000
分区:医学2区 Top / 生化与分子生物学2区 生物物理2区 肿瘤学2区
发表日期:2024 Nov
作者:
Feifei Teng, Xiao Ju, Zhenhua Gao, Junhao Xu, Yikun Li, Yungang Wang, Bingwen Zou, Jinming Yu
摘要
鉴于免疫疗法在晚期疾病中导致了显着的总体生存率（OS）益处，因此确定这些药物在早期非小细胞肺癌（NSCLC）中的有效性引人注目。在早期NSCLC中，具有免疫治疗方法的潜在潜在，以反映高级NSCLC中看到的范式，其中生存增强能力显着使大多数患者受益。 However, their performance in early-stage epidermal growth factor receptor (EGFR) mutant NSCLC is controversial.在包括EGFR突变状态的患者的有限研究中，我们发现围手术期免疫检查点抑制剂（ICI）在可切除的EGFR阳性NSCLC中的出乎意料，良好的生存益处，这与先进的EGFR-Mutant NSCLC中的患者有争议。 It is possible because of the shift toward immunosuppression that the immune environment undergoes during tumor progression. In the early disease stages, the anti-tumor immune response can be activated with fewer hindrances. In the context of EGFR mutant tumors, intratumor genetic heterogeneity can generate treatment-sensitive and -resistant subclones.抗性亚克隆的亚克隆性在治疗反应中至关重要，酪氨酸激酶抑制剂（TKIS）有选择地控制EGFR-突变细胞增殖和“竞争性释放”，从而有可能解释辅助TKIS试验中的较低病理反应。这篇评论研究了早期EGFR突变体NSCLC的围手术期治疗方式的新兴数据，探索了独特的机制和预测性生物标志物，以指导围手术期管理策略。
Abstract
Given that immunotherapy has resulted in a significant overall survival (OS) benefit in advanced-stage disease, it is of notable interest to determine the effectiveness of these agents in early-stage non-small cell lung cancer (NSCLC). The potential exists for the immunotherapeutic approach in early-stage NSCLC to mirror the paradigm seen in advanced NSCLC, wherein survival enhancements have notably benefited the majority of patients. However, their performance in early-stage epidermal growth factor receptor (EGFR) mutant NSCLC is controversial. In the limited studies that included patients with EGFR mutation status, we found unexpected, good survival benefits of perioperative immune checkpoint inhibitors (ICIs) in resectable EGFR-positive NSCLC, which is controversial with those in advanced EGFR-mutant NSCLC. It is possible because of the shift toward immunosuppression that the immune environment undergoes during tumor progression. In the early disease stages, the anti-tumor immune response can be activated with fewer hindrances. In the context of EGFR mutant tumors, intratumor genetic heterogeneity can generate treatment-sensitive and -resistant subclones. The subclonality of the resistant subclone is pivotal in therapy response, with tyrosine kinase inhibitors (TKIs) selectively controlling EGFR-mutant cell proliferation and "competitive release" potentially explaining lower pathological responses in adjuvant TKIs trials. This review delves into emerging data on perioperative treatment modalities for early-stage EGFR mutant NSCLC, exploring unique mechanisms and predictive biomarkers to guide perioperative management strategies.