围手术期免疫治疗在EGFR突变非小细胞肺癌患者中的潜在意外益处
Perioperative immunotherapy for patients with EGFR mutant non-small cell lung cancer: Unexpected potential benefits
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影响因子:8.3
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
DOI:
10.1016/j.bbcan.2024.189194
摘要
鉴于免疫治疗在晚期疾病中显著改善总生存期（OS），研究其在早期非小细胞肺癌（NSCLC）中的疗效具有重要意义。早期NSCLC采用免疫疗法的潜力可能类似于晚期NSCLC，在后者中，生存改善已明显惠及大部分患者。然而，免疫治疗在早期表皮生长因子受体（EGFR）突变NSCLC中的表现存在争议。在有限的研究中，包含EGFR突变状态患者的数据显示，手术切除的EGFR阳性NSCLC中围手术期免疫检查点抑制剂（ICIs）意外地带来了良好的生存益处，这与晚期EGFR突变NSCLC中的结果存在争议。这可能是由于肿瘤进展过程中免疫环境的向免疫抑制转变。在早期疾病阶段，抗肿瘤免疫反应可以在较少障碍的情况下激活。在EGFR突变肿瘤的背景下，肿瘤内遗传异质性可能导致治疗敏感和耐药的亚克隆。耐药亚克隆的亚克隆性在治疗反应中起关键作用，酪氨酸激酶抑制剂（TKIs）选择性控制EGFR突变细胞增殖，“竞争释放”可能解释了辅助治疗TKIs试验中较低的病理反应。本文探讨了早期EGFR突变NSCLC围手术期治疗新数据，分析了其独特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.