Single-cell transcriptional profiling uncovers the association between EOMES+CD8+ T cells and acquired EGFR-TKI resistance

Guosheng Wang; Jiaxing Sun; Jing Zhang; Qiping Zhu; Jingjing Lu; Shaoyong Gao; Feilong Wang; Qi Yin; Yuan Wan; Qiang Li

doi:10.1016/j.drup.2022.100910

Single-cell transcriptional profiling uncovers the association between EOMES⁺CD8⁺ T cells and acquired EGFR-TKI resistance

Drug Resist Updat. 2023 Jan:66:100910. doi: 10.1016/j.drup.2022.100910. Epub 2022 Dec 15.

Authors

Guosheng Wang¹, Jiaxing Sun², Jing Zhang³, Qiping Zhu⁴, Jingjing Lu³, Shaoyong Gao³, Feilong Wang⁵, Qi Yin⁶, Yuan Wan⁷, Qiang Li⁸

Affiliations

¹ Department 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. Electronic address: gswang@tongji.edu.cn.
² Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.
³ Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
⁴ Department of Pathology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
⁵ Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China. Electronic address: wang_feilong@tongji.edu.cn.
⁶ Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China. Electronic address: yvonneyinqi2019@126.com.
⁷ The Pq Laboratory of Micro/Nano BiomeDx, Department of Biomedical Engineering, Binghamton University-SUNY, Binghamton, NY 13902, United States. Electronic address: ywan@binghamton.edu.
⁸ Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China. Electronic address: liqressh@hotmail.com.

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.

Keywords: Biomarker; EGFR-TKI resistance; EOMES; Lung cancer; Single-cell analysis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes*
Drug Resistance, Neoplasm / genetics
ErbB Receptors / genetics
Humans
Lung Neoplasms* / drug therapy
Mutation
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use
T-Box Domain Proteins / genetics
T-Box Domain Proteins / therapeutic use

Substances

Protein Kinase Inhibitors
ErbB Receptors
EOMES protein, human
T-Box Domain Proteins
EGFR protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding