Tumor-associated macrophages mediate resistance of EGFR-TKIs in non-small cell lung cancer: mechanisms and prospects

Front Immunol. 2023 Aug 15:14:1209947. doi: 10.3389/fimmu.2023.1209947. eCollection 2023.

Abstract

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the first-line standard treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation. However, resistance to EGFR-TKIs is inevitable. Currently, most studies on the mechanism of EGFR-TKIs resistance mainly focus on the spontaneous resistance phenotype of NSCLC cells. Studies have shown that the tumor microenvironment (TME) also mediates EGFR-TKIs resistance in NSCLC. Tumor-associated macrophages (TAMs), one of the central immune cells in the TME of NSCLC, play an essential role in mediating EGFR-TKIs resistance. This study aims to comprehensively review the current mechanisms underlying TAM-mediated resistance to EGFR-TKIs and discuss the potential efficacy of combining EGFR-TKIs with targeted TAMs therapy. Combining EGFR-TKIs with TAMs targeting may improve the prognosis of NSCLC with EGFR mutation to some extent.

Keywords: EGFR-TKIs; NSCLC; exosome; resistance; tumor-associated macrophages.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Drug Resistance, Neoplasm
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms* / drug therapy
  • Mutation
  • Tumor Microenvironment
  • Tumor-Associated Macrophages
  • Tyrosine Kinase Inhibitors* / therapeutic use

Substances

  • EGFR protein, human
  • ErbB Receptors
  • Tyrosine Kinase Inhibitors

Grants and funding

This study was supported by the Science and Technology Project for Youth Talent of Changzhou Health Commission (QN201703), Young Talent Development Plan of Changzhou Health Commission (CZQM2020024), Major Science and Technology Project of Changzhou Health Commission (ZD202004, ZD202007), and China Postdoctoral Science Foundation (2020M670064ZX).