早期肺腺癌不同EGFR突变亚型的独特空间免疫微环境特征
Distinct spatial immune microenvironment features of different EGFR mutation subtypes in early-stage lung adenocarcinoma.
作者
作者单位
- Department of Thoracic Surgery, Peking University People's Hospital, Beijing 100044, China; Thoracic Oncology Institute & Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Peking University People's Hospital, Beijing 100044, China; Institute of Advanced Clinical Medicine, Peking University, Beijing 100191, China.
- Department of Thoracic Surgery, Peking University People's Hospital, Beijing 100044, China; Thoracic Oncology Institute & Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Peking University People's Hospital, Beijing 100044, China.
- Department of Thoracic Surgery, Peking University People's Hospital, Beijing 100044, China.
- Chinese Institutes for Medical Research, Beijing 100069, China.
- Chinese Institutes for Medical Research, Beijing 100069, China; College of Artificial Intelligence, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.
- Department of Thoracic Surgery, Peking University People's Hospital, Beijing 100044, China; Thoracic Oncology Institute & Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Peking University People's Hospital, Beijing 100044, China; Institute of Advanced Clinical Medicine, Peking University, Beijing 100191, China. Electronic address: chenkezhong@pkuph.edu.cn.
- Department of Thoracic Surgery, Peking University People's Hospital, Beijing 100044, China; Thoracic Oncology Institute & Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Peking University People's Hospital, Beijing 100044, China; Institute of Advanced Clinical Medicine, Peking University, Beijing 100191, China. Electronic address: haolipkuph@pku.edu.cn.
摘要
中文
表皮生长因子受体（EGFR）突变在肺腺癌（LUAD）中常见，但它们对早期疾病中空间肿瘤免疫微环境（TIME）的影响仍不清楚。我们使用整合基因组测序和多重免疫组织化学（mIHC）表征了144例未经治疗的早期LUAD中的空间TIME。尽管EGFR突变肿瘤总体显示出与EGFR野生型肿瘤相比减少的CD8+ T细胞浸润，但在EGFR亚型中观察到显著异质性。具体来说，与19del亚型相比，L858R和罕见变异亚型表现出更高的肿瘤突变负荷、更大的CD8+ T细胞密度，以及T细胞为主的细胞邻域富集，与相对免疫浸润的表型一致。相反，19del肿瘤表现出较低的T细胞浸润。TP53共突变也与增强的CD8+ T细胞浸润相关。这些横断面发现确定了跨EGFR突变LUAD亚型的假设生成的空间免疫表型；它们与围手术期治疗选择的潜在相关性需要在具有结果注释的治疗队列中进行前瞻性验证。
English
Epidermal growth factor receptor (EGFR) mutations are common in lung adenocarcinoma (LUAD), yet their influence on the spatial tumor immune microenvironment (TIME) in early-stage disease remains unclear. We characterized the spatial TIME in 144 treatment-naïve, early-stage LUADs using integrated genomic sequencing and multiplex immunohistochemistry (mIHC). Although EGFR-mutant tumors overall displayed reduced CD8 + T-cell infiltration compared with EGFR-wild-type tumors, substantial heterogeneity was observed among EGFR subtypes. Specifically, L858R and rare-variant subtypes exhibited higher tumor mutational burden, greater CD8 + T-cell density, and enrichment of T-cell-dominant cellular neighborhoods relative to 19del subtype, consistent with a comparatively immune-infiltrated phenotype. In contrast, 19del tumors showed lower T-cell infiltration. TP53 co-mutation was also associated with enhanced CD8 + T-cell infiltration. These cross-sectional findings identify hypothesis-generating spatial immune phenotypes across EGFR-mutant LUAD subtypes; their potential relevance to perioperative treatment selection requires prospective validation in outcome-annotated treatment cohorts.
分类与指标
- 研究类型
- 基础研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 5.3
- 新锐分区
- 2区