Available online 13 November 2023, 101019

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This report expands on our previous research, highlighting a unique inverse correlation between MYC expression in tumor cells and immune cells during the development of EGFR-TKI resistance. It is observed that MYC expression and fatty acid oxidation (FAO) metabolism in tissue-resident memory (TRM) CD8+ T cells are significantly impaired. These findings offer new insights into the mechanisms of TKI resistance. Although the study is preliminary, it suggests caution when interpreting the effectiveness of MYC inhibitors in reversing TKI resistance, especially when immune factors are not considered.

Section snippetsClinical Samples and Methodology

Single-cell data analysis and clinical samples collection from 17 patients (RD, n=10; PD, n=7) were performed referred to our previous study (Wang et al., 2023). In this study, multicolor immunofluorescence analyses was utilized to scrutinize the expression of various markers in paraffin-embedded tissue sections. Initially, the sections underwent a process of dewaxing and hydration, followed by antigen retrieval. To inhibit non-specific binding, the sections were blocked with 2% Bovine Serum

Ethics approval and consent to participate

Ethical approval was granted by the Ethics Committee of Shanghai East Hospital.

Consent for publication

Not applicable

Funding

This work was supported by NCI 1R01CA230339-01 subaward and The Outstanding Clinical Discipline Project of Shanghai Pudong. This work was also supported by Project A: Project number: MA2021021 of Nantong Municipal Health Commission, Project number: Z2022036 of Jiangsu Provincial Health Commission and Special Key Project of Clinical Medicine of Nantong University (2022JZ012).

CRediT authorship contribution statement

Funding acquisition: QL, YW and TL; investigation: GW and TL; writing: GW. All authors have read and agreed to the published version of this manuscript.

Declaration of Competing Interest

The authors declare no conflict of interest.

Acknowledgments

The authors greatly thank Ashley Maynard, Collin M. Blakely, Spyros Darmanis, and Trever G. Bivona for their support. The authors would like to thank Yue Zhang, and Xiaoqing Ma for their valuable help.

Conflicts of Interest

The authors declare no conflict of interest.

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