Related Experiment Video
Updated: Dec 7, 2025
In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
Favorable Immune Microenvironment in Patients with EGFR and MAPK Co-Mutations
Wang Yang1, Naifei Chen1, Lingyu Li1
1The Cancer Center of the First Hospital of Jilin University, Changchun, Jilin 130021, People's Republic of China.
Purpose:
Although EGFR-mutated patients generally do not benefit from checkpoint inhibitors (ICIs), some patients in the KEYNOTE-001 study consistently benefited from this treatment. This study investigated immune microenvironment characteristics to identify the subgroup of patients that may benefit from ICIs.
Materials And Methods:
Using data from The Cancer Genome Atlas Program (TCGA) and Cancer Proteome Atlas, TMB and protein level of PD-L1 were explored in the patients with EGFR mutations and wild-type patients. Different patterns of EGFR mutations (according to EGFR co-mutation with different downstream pathway genesets) were used to group EGFR mutation population. Estimated infiltration analyses were used to explore changes in the immune microenvironment.
Results:
This study analyzed somatic mutation data from 1287 patients from five cohorts (TCGA, Broad, The Tumour Sequencing Project, Memorial Sloan Kettering Cancer Center, Catalogue Of Somatic Mutations In Cancer database). The probability of EGFR mutation was approximately 14.30% (184/1287) and the co-mutation rate was 11.41% (21/184) in patients with EGFR mutations. Glycosaminoglycan-related pathways were significantly upregulated in the EGFR mutant group. EGFR-mutated patients had lower TMB and PD-L1 protein levels than those in wild-type patients. Increase immature DCs infiltration and decreased NK CD56dim, T gamma delta, cytotoxic, and Th2 cell infiltration were the main immune changes in EGFR-mutated patients. Patients with EGFR-MAPK co-mutations had higher levels of TMB and PD-L1 protein expression. Meanwhile, the co-mutated patients had a similar immune microenvironment as that in wild-type patients.
Conclusion:
In this study, we defined a subgroup of patients with EGFR-MAPK co-mutations. These co-mutated patients may benefit from ICI treatment.
Insights
Certain EGFR-mutated patients may benefit from immune checkpoint inhibitors (ICIs). Patients with EGFR-MAPK co-mutations show potential for ICI therapy due to a favorable immune microenvironment.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Immune checkpoint inhibitors (ICIs) are generally ineffective in EGFR-mutated cancers.
- Some EGFR-mutated patients paradoxically benefit from ICIs, suggesting specific subgroups may respond.
Purpose of the Study:
- To investigate immune microenvironment characteristics in EGFR-mutated patients.
- To identify a subgroup of EGFR-mutated patients who may benefit from ICIs.
Main Methods:
- Analysis of somatic mutation data from TCGA and other databases (1287 patients).
- Exploration of Tumor Mutational Burden (TMB) and PD-L1 protein levels.
- Assessment of immune cell infiltration patterns based on EGFR mutation status and co-mutations.
Main Results:
- EGFR mutations occurred in 14.30% of patients; co-mutation rate was 11.41%.
- EGFR-mutated patients had lower TMB and PD-L1 levels compared to wild-type.
- EGFR-MAPK co-mutations were associated with higher TMB, PD-L1 expression, and an immune microenvironment similar to wild-type patients.
Conclusions:
- A subgroup of patients with EGFR-MAPK co-mutations was identified.
- These EGFR-MAPK co-mutated patients represent a potential population that could benefit from ICI treatment.
Related Concept Videos
02:38Mitogens and the Cell Cycle
02:17The Tumor Microenvironment
01:27Tumor Immunotherapy
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...