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Updated: Nov 2, 2025
Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
Published on: June 7, 2018
Exploration of the Tumor-Suppressive Immune Microenvironment by Integrated Analysis in EGFR-Mutant Lung
Teng Li1, Xiaocong Pang2, Junyun Wang3,4
1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background:
Clinical evidence has shown that few non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations can benefit from immunotherapy. The tumor immune microenvironment (TIME) is a significant factor affecting the efficacy of immunotherapy. However, the TIME transformational process in EGFR-mutation patients is unknown.
Methods:
The mRNA expression and mutation data and lung adenocarcinoma (LUAD) clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Profiles describing the immune landscape of patients with EGFR mutations were characterized by differences in tumor mutation burden (TMB), ESTIMATE, CIBERSORT, and microenvironment cell populations-counter (MCP-counter).
Results:
In total, the TCGA data for 585 patients were analyzed. Among these patients, 98 had EGFR mutations. The TMB was lower in the EGFR group (3.94 mut/Mb) than in the KRAS mutation group (6.09 mut/Mb, P < 0.001) and the entire LUAD (6.58 mut/Mb, P < 0.001). The EGFR group had a lower population of activated immune cells and an even higher score of immunosuppressive cells. A further inter-group comparison showed that differences in the TMB and tumor-infiltrating lymphocytes were only found between patients with oncogenic mutations and unknown mutation. Meanwhile, there were more myeloid dendritic cells (DCs) in EGFR 19del than in L858R-mutation patients and in common mutation patents than in uncommon mutation patients (P < 0.05). Additionally, we established a D score, where D = MCP-counter score for cytotoxic T lymphocytes (CTLs)/MCP-counter score for myeloid DCs. Further analysis revealed that lower D scores indicated immune suppression and were negatively related to several immunotherapy biomarkers.
Conclusions:
The TIME of EGFR mutant NSCLC was immunosuppressive. Myeloid DCs gradually increased in EGFR 19del, L858R, and uncommon mutations. The potential role of CTLs and DCs in the TIME of patients requires further investigation.
Insights
Patients with EGFR-mutant non-small cell lung cancer have an immunosuppressive tumor immune microenvironment (TIME). This study characterized TIME in EGFR-mutant NSCLC, revealing lower tumor mutation burden and increased immunosuppressive cells, impacting immunotherapy efficacy.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Limited benefit from immunotherapy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations.
- Tumor immune microenvironment (TIME) significantly influences immunotherapy efficacy.
- The TIME transformation in EGFR-mutant NSCLC remains poorly understood.
Purpose of the Study:
- To characterize the TIME in EGFR-mutant NSCLC.
- To investigate immune landscape differences based on EGFR mutation status.
- To identify potential biomarkers for immunotherapy response.
Main Methods:
- Analysis of mRNA expression, mutation data, and clinical data from The Cancer Genome Atlas (TCGA) database for lung adenocarcinoma (LUAD).
- Characterization of immune profiles using tumor mutation burden (TMB), ESTIMATE, CIBERSORT, and microenvironment cell populations-counter (MCP-counter).
- Establishment of a D score (cytotoxic T lymphocytes/myeloid dendritic cells) to assess immune suppression.
Main Results:
- Analysis of 585 LUAD patients, including 98 with EGFR mutations.
- Lower TMB in EGFR-mutant group compared to KRAS-mutant and overall LUAD cohorts.
- Increased immunosuppressive cells and decreased activated immune cells observed in EGFR-mutant patients.
- Myeloid dendritic cell populations increased in specific EGFR mutation subtypes (19del, L858R, uncommon mutations).
- Lower D scores correlated with immune suppression and negatively with immunotherapy biomarkers.
Conclusions:
- The TIME in EGFR-mutant NSCLC is characterized by immunosuppression.
- Myeloid dendritic cells show a gradual increase across different EGFR mutation types.
- Further research is needed to elucidate the roles of cytotoxic T lymphocytes (CTLs) and dendritic cells (DCs) in the TIME of these patients.
