Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China; Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, China.
Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Clin Lung Cancer. 2018 Sep;19(5):e551-e558. doi: 10.1016/j.cllc.2018.03.011. Epub 2018 Mar 17.
The benefits of immune checkpoint inhibitors for first-line treatment in patients with lung adenocarcinoma harboring EGFR mutations are unclear. The effects of ICIs depend on the tumor microenvironment (TME). Differences in TME properties between mutant and wild-type EGFR have not been fully characterized.
We collected 105 surgically resected (50 EGFR mutated and 55 EGFR wild-type), treatment-naïve lung adenocarcinoma tissues with clinical data to investigate the landscape and compartmentalization of tumor-infiltrating immune cells with respect to EGFR status by immunohistochemistry. The normalized FPKM values of data for 531 patients were obtained from The Cancer Genome Atlas (TCGA) Data Portal (https://portal.gdc.cancer.gov/).
CD68-positive cells within the tumor niche exhibited more intensive infiltration in wild-type EGFR than in mutations, and was related to lymph node invasion. In the RNA-Seq analysis, MMP9 and VEGFA showed higher levels in wild-type EGFR than in mutant cases. The EGFR mutation independently predicted a favorable disease-free survival.
The CD68-positive cells play a crucial role in discriminating the TME between different EGFR statuses.
对于携带 EGFR 突变的肺腺癌患者，免疫检查点抑制剂作为一线治疗的获益尚不清楚。ICIs 的效果取决于肿瘤微环境（TME）。EGFR 突变型和野生型之间 TME 特性的差异尚未得到充分描述。
我们收集了 105 例手术切除的（50 例 EGFR 突变和 55 例 EGFR 野生型）、未经治疗的肺腺癌组织，并结合临床数据，通过免疫组织化学方法，针对 EGFR 状态，研究肿瘤浸润免疫细胞的分布和区室化情况。从癌症基因组图谱（TCGA）数据门户（https://portal.gdc.cancer.gov/）获得了 531 例患者的 531 个数据的标准化 FPKM 值。
肿瘤巢内 CD68 阳性细胞的浸润在野生型 EGFR 中比在突变中更强烈，并且与淋巴结浸润有关。在 RNA-Seq 分析中，MMP9 和 VEGFA 在野生型 EGFR 中表达水平更高。EGFR 突变独立预测了良好的无病生存。
CD68 阳性细胞在区分不同 EGFR 状态的 TME 方面起着关键作用。
