Emerging role of egfr mutations in creating an immune suppressive tumour microenvironment

Simran S. Kapoor, Dietmar M.W. Zaiss*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Several types of tumours overexpress the Epidermal Growth Factor Receptor (EGFR) in either wild type or mutated form. These tumours are often highly aggressive and difficult to treat. The underlying mechanisms for this phenomenon have remained largely unresolved, but recent publications suggest two independent mechanisms that may contribute. According to one line of research, tumours that overexpress the EGFR grow autonomously and become “addicted” to growth factor signalling. Inhibition of this signal using EGFR inhibitors can, therefore, induce cell death in tumour cells and lead to tumour shrinkage. The other line of research, as highlighted by recent findings, suggests that the overexpression, specifically of mutant forms of the EGFR, may create an immune-suppressive and lymphocyte depleted microenvironment within tumours. Such a lymphocyte depleted microenvironment may explain the resistance of EGFR overexpressing cancers to tumour therapies, particularly to check-point inhibitor treatments. In this article, we discuss the recent data which support an immune modulatory effect of EGFR signalling and compare these published studies with the most recent data from The Cancer Genome Atlas (TCGA), in this way, dissecting possible underlying mechanisms. We thereby focus our study on how EGFR overexpression may lead to the local activation of TGFβ, and hence to an immune suppressive environment. Consequently, we define a novel concept of how the mitogenic and immune modulatory effects of EGFR overexpression may contribute to tumour resistance to immunotherapy, and how EGFR specific inhibitors could be used best to enhance the efficacy of tumour therapy.

Original languageEnglish
Article number52
Number of pages11
JournalBiomedicines
Volume10
Issue number1
Early online date27 Dec 2021
DOIs
Publication statusE-pub ahead of print - 27 Dec 2021

Keywords

  • epidermal growth factor receptor (EGFR)
  • immune checkpoint inhibitors (ICI)
  • lymphocyte depletion
  • transforming growth factor beta (TGFβ)
  • tumour immunotherapy
  • tumour microenvironment (TME)

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