Related Experiment Video
Updated: Nov 26, 2025
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
EPHA5 mutations predict survival after immunotherapy in lung adenocarcinoma
Zhiming Chen1, Ji Chen2, Dandan Ren3
1Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Abstract:
Eph receptors constitute the largest family of RTKs, and their associations with antitumor immunity and immunotherapy are largely unknown. By integrating genomic, transcriptomic and clinical data from cohorts in public databases, we identified EPHA5 as the most common mutated gene of Eph receptors in lung adenocarcinoma (LUAD). Moreover, compared with EPHA5 wild-type (WT) patients, EPHA5-mutant (Mut) patients exhibited significantly enhanced infiltration of CD8+ T cells and M1 macrophages, reduced recruitment of immunosuppressive regulatory T cells (Tregs) into the tumor site, as well as the increased level of chemokine, interferon-gamma, inhibitory immune checkpoint signatures, tumor mutation burden (TMB) and tumor neoantigen burden (TNB). Additionally, EPHA5 mutation cooccurred with homologous recombination (HR) or mismatch repair (MMR) gene mutations. These data were validated in the LUAD cell line H1299 and a Chinese LUAD cohort. Most importantly, clinical analysis of a Memorial Sloan Kettering Cancer Center (MSKCC) immunotherapy cohort indicated that LUAD patients with EPHA5 mutations who were treated with immunotherapy had markedly prolonged survival times. Our results revealed the correlation of EPHA5 mutations with tumor immune microenvironment and predictive factors for immunotherapy, implying the potential of EPHA5 mutations as a prognostic marker for the prognosis of LUAD patients to immune checkpoint blockade therapy.
Insights
Ephrin receptor A5 (EPHA5) mutations are common in lung adenocarcinoma (LUAD). These mutations enhance anti-tumor immunity and predict better survival in patients treated with immunotherapy, suggesting EPHA5 as a potential prognostic marker.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Eph receptors, a large receptor tyrosine kinase (RTK) family, have largely unknown roles in antitumor immunity and immunotherapy.
- Lung adenocarcinoma (LUAD) is a major form of lung cancer with complex interactions between tumor cells and the immune microenvironment.
Purpose of the Study:
- To investigate the role of Eph receptors, specifically EPHA5, in the tumor immune microenvironment of LUAD.
- To determine if EPHA5 mutations can serve as predictive biomarkers for immunotherapy response in LUAD patients.
Main Methods:
- Integrated analysis of genomic, transcriptomic, and clinical data from public LUAD cohorts.
- Validation using LUAD cell lines and an independent Chinese LUAD cohort.
- Analysis of an immunotherapy cohort from Memorial Sloan Kettering Cancer Center (MSKCC).
Main Results:
- EPHA5 was identified as the most frequently mutated Eph receptor in LUAD.
- EPHA5 mutations correlated with increased CD8+ T cell and M1 macrophage infiltration, decreased regulatory T cell (Treg) recruitment, and elevated tumor mutational burden (TMB) and neoantigen burden (TNB).
- EPHA5 mutations were associated with improved survival in LUAD patients undergoing immunotherapy and co-occurred with homologous recombination (HR) or mismatch repair (MMR) gene mutations.
Conclusions:
- EPHA5 mutations significantly shape the LUAD immune microenvironment.
- EPHA5 mutations are potential predictive biomarkers for immunotherapy efficacy, particularly immune checkpoint blockade therapy.
- EPHA5 mutations may serve as a prognostic marker for LUAD patients receiving immunotherapy.
Related Concept Videos
02:38Mitogens and the Cell Cycle
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal