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Updated: Feb 12, 2026

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Tumor Microenvironment Properties are Associated With Low CD68-positive Cell Infiltration and Favorable Disease-free
Zhihua Gong1, Junying Chen1, Jia-Nan Cheng1
1Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China; Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, China.
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.
Insights
Immune checkpoint inhibitors
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- The efficacy of immune checkpoint inhibitors (ICIs) as first-line treatment for lung adenocarcinoma with EGFR mutations remains uncertain.
- Tumor microenvironment (TME) characteristics significantly influence ICI response.
- Distinct TME properties between EGFR-mutant and wild-type lung adenocarcinomas are not well-defined.
Purpose of the Study:
- To investigate the differences in tumor-infiltrating immune cells based on EGFR mutation status in lung adenocarcinoma.
- To characterize the tumor microenvironment (TME) landscape in relation to EGFR mutations.
- To explore the prognostic implications of EGFR status in lung adenocarcinoma.
Main Methods:
- Analysis of 105 surgically resected, treatment-naïve lung adenocarcinoma tissues (50 EGFR mutated, 55 EGFR wild-type) using immunohistochemistry.
- Assessment of tumor-infiltrating immune cells and TME composition.
- Utilized RNA-Seq data from The Cancer Genome Atlas (TCGA) for 531 patients.
Main Results:
- CD68-positive cell infiltration was higher in wild-type EGFR tumors compared to mutant EGFR tumors, correlating with lymph node invasion.
- RNA-Seq analysis revealed elevated MMP9 and VEGFA levels in wild-type EGFR cases versus mutant EGFR cases.
- EGFR mutation status was an independent predictor of favorable disease-free survival.
Conclusions:
- CD68-positive cells are key discriminators of the tumor microenvironment (TME) between EGFR-mutant and wild-type lung adenocarcinoma.
- Understanding TME differences based on EGFR status is crucial for optimizing treatment strategies, including immune checkpoint inhibitors.
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