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Single-cell transcriptional profiling uncovers the association between EOMES+CD8+ T cells and acquired EGFR-TKI
Guosheng Wang1, Jiaxing Sun2, Jing Zhang3
1Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; The Pq Laboratory of Micro/Nano BiomeDx, Department of Biomedical Engineering, Binghamton University-SUNY, Binghamton, NY 13902, United States.
Abstract:
Acquired resistance to tyrosine kinase inhibitors (TKIs) is reportedly inevitable in lung cancers harboring epidermal growth factor receptor (EGFR) mutations, emphasizing the need for novel approaches to predict EGFR-TKI resistance for clinical monitoring and patient management. This study identified a significant increase in eomesodermin (EOMES)+CD8+ T cells in the TKI-resistant patients, which was correlated with poor survival. The increase in EOMES+CD8+ T cells was further confirmed in both tissue samples and peripheral blood of patients with TKIs resistance. The integrated analysis of pseudotime and Gene set variation showed that the increase in EOMES+CD8+ T cells may be attributed to TRM T cell conversion and metabolic reprogramming. Overall, this work suggested an association between the increased number of EOMES+CD8+ T cells and acquired TKI drug resistance, supporting the utility of EOMES+CD8+ T cells as a biomarker for TKI treatment response.
Insights
Increased eomesodermin (EOMES)+CD8+ T cells indicate acquired resistance to tyrosine kinase inhibitors (TKIs) in lung cancer. These cells may serve as a predictive biomarker for TKI treatment response and patient survival.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Acquired resistance to tyrosine kinase inhibitors (TKIs) is a significant challenge in treating lung cancers with epidermal growth factor receptor (EGFR) mutations.
- Predicting and managing EGFR-TKI resistance is crucial for effective clinical monitoring and patient care.
Purpose of the Study:
- To identify potential biomarkers for predicting acquired resistance to EGFR-TKIs in lung cancer.
- To investigate the role of specific immune cell populations in the development of TKI resistance.
Main Methods:
- Analysis of eomesodermin (EOMES)+CD8+ T cell populations in TKI-resistant lung cancer patients.
- Confirmation of findings in both tumor tissue samples and peripheral blood.
- Integrated analysis using pseudotime and Gene set variation to explore underlying mechanisms.
Main Results:
- A significant increase in EOMES+CD8+ T cells was observed in patients with acquired TKI resistance.
- Elevated EOMES+CD8+ T cells correlated with poorer patient survival.
- Findings were consistent across both tissue and blood samples.
Conclusions:
- Increased EOMES+CD8+ T cells are associated with acquired TKI drug resistance in EGFR-mutated lung cancer.
- EOMES+CD8+ T cells show potential as a predictive biomarker for TKI treatment response.
- Further research into T cell conversion and metabolic reprogramming may elucidate resistance mechanisms.
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