Zhihua Gong1, Junying Chen1, Jia-Nan Cheng1, Chengdu Sun1, Qingzhu Jia1, Xinwei Diao2, Bo Zhu3. 1. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China; Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, China. 2. Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing, China. 3. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China; Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, China. Electronic address: bo.zhu@tmmu.edu.cn.
Abstract
BACKGROUND: 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. PATIENTS AND METHODS: 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/). RESULTS: 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. CONCLUSION: The CD68-positive cells play a crucial role in discriminating the TME between different EGFR statuses.
BACKGROUND: 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. PATIENTS AND METHODS: 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/). RESULTS: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. CONCLUSION: The CD68-positive cells play a crucial role in discriminating the TME between different EGFR statuses.