Recent clinical trials of lung adenocarcinoma with immune checkpoint inhibitors revealed that lung adenocarcinoma patients with EGFR mutations have a poor response to immunotherapy. However, the mechanisms have not been addressed. We performed immunohistochemistry analyses of resected lung adenocarcinoma tissues with and without EGFR mutations to investigate and compare the characteristics of the tumor microenvironment (TME). We retrospectively enrolled a total of 323 lung adenocarcinoma patients (164 had EGFR mutations), and their corresponding tissue samples were analyzed by the EGFR mutation test and immunohistochemistry. We selected the markers of the immune checkpoint molecule (PD1, PD-L1, and LAG-3) and immune cell (CD3, CD4, CD8, and Foxp3) as markers of the tumor microenvironment. Our results revealed that patients had a distinct tumor microenvironment between EGFR-mutant and wild-type lung adenocarcinomas; the expression of CD3, CD4, PD-L1, and Foxp3 in EGFR-mutant tumors was significantly higher than that in wild-type tumors, while the expression of LAG3 and PD-1 showed a positive correlation with EGFR-wild-type tumors. In survival analysis, EGFR-wild-type patients had longer disease-free survival (DFS) than EGFR-mutant patients (). Our research demonstrates significant differences in tumor microenvironment composition between EGFR-mutant and wild-type patients. Our findings provide novel evidence that contributes to understanding the mechanism underlying the poor efficacy of immune checkpoint inhibitors.

中文翻译：

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EGFR突变和野生型肺腺癌之间的免疫学差异

最近使用免疫检查点抑制剂进行的肺腺癌临床试验显示，具有EGFR突变的肺腺癌患者对免疫治疗的反应较差。然而，这些机制尚未得到解决。我们对切除的有和没有EGFR突变的肺腺癌组织进行了免疫组织化学分析，以研究和比较肿瘤微环境 (TME) 的特征。我们回顾性招募了 323 例肺腺癌患者（164 例有EGFR突变），并通过EGFR分析了他们相应的组织样本。突变检测和免疫组化。我们选择免疫检查点分子（PD1、PD-L1和LAG-3）和免疫细胞（CD3、CD4、CD8和Foxp3）的标志物作为肿瘤微环境的标志物。我们的研究结果表明，患者在EGFR突变型和野生型肺腺癌之间具有不同的肿瘤微环境；EGFR突变型肿瘤中CD3、CD4、PD-L1和Foxp3的表达明显高于野生型肿瘤，而LAG3和PD-1的表达与EGFR野生型肿瘤呈正相关。在生存分析中，EGFR野生型患者的无病生存期（DFS）比EGFR突变型患者更长（）。我们的研究表明EGFR突变型和野生型患者的肿瘤微环境组成存在显着差异我们的研究结果提供了新的证据，有助于理解免疫检查点抑制剂疗效不佳的机制。