Mathematical investigation of innate immune responses to lung cancer: the role of macrophages with mixed phenotypes

Raluca Eftimie (Lead / Corresponding author), Charlotte Barelle

Research output: Contribution to journalArticlepeer-review

Abstract

Macrophages' role in the evolution of solid tumours is a well accepted fact, with the M1-like macrophages having an anti-tumour role and the M2-like macrophages having a pro-tumour role. Despite the fact that some clinical studies on lung tumours have emphasised also the presence of macrophages with mixed M1 and M2 phenotypes in addition to macrophages with distinct phenotypes, the majority of studies still use the distinct M1-M2 classification to predict the evolution of tumours and patient survival. In this theoretical study we use a mathematical modelling and computational approach to investigate the role of macrophages with mixed phenotype on growth/control/elimination of lung tumours. We show that tumour control in the presence of M2→M1 re-polarising treatments is mainly the result of macrophages with mixed phenotypes (due to the assumption of short half-life of M1-like macrophages). We also show that the half-life of various macrophage phenotypes (distinct M1 or mixed M1/M2 phenotypes) impacts the outcome of various therapeutic strategies targeting tumour-associated macrophages. All these results suggest the need for a better experimental understanding of the kinetics of macrophages inside solid tumours.

Original languageEnglish
Article number110739
Number of pages14
JournalJournal of Theoretical Biology
Volume524
Early online date28 Apr 2021
DOIs
Publication statusPublished - 7 Sep 2021

Keywords

  • Mathematical modelling
  • Non-small cell lung cancer
  • M1 and M2 macrophages
  • Macrophages with mixed phenotypes

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