Abstract
Lung cancer is the leading cause of death from cancer worldwide. Recent studies demonstrated that the tumour microenvironment (TME) is pivotal for tumour progression, providing multiple targeting opportunities for therapeutic strategies. As one of the most abundant stromal cell types in the TME, tumour-associated macrophages (TAMs) exhibit high plasticity. Malignant cells alter their metabolic profiles to adapt to the limited availability of oxygen and nutrients in the TME, resulting in functional alteration of TAMs. The metabolic features of TAMs are strongly associated with their functional plasticity, which further impacts metabolic profiling in the TME and contributes to tumourigenesis and progression. Here, we review the functional determination of the TME by TAM metabolic alterations, including glycolysis as well as fatty acid and amino acid metabolism, which in turn are influenced by environmental changes. Additionally, we discuss metabolic reprogramming of TAMs to a tumouricidal phenotype as a potential antitumoural therapeutic strategy.
Abstract
Tumour-associated macrophages (TAMs) display a high level of functional plasticity and altered metabolism symbolised by high sensitivity to the surrounding tumour microenvironment. The metabolism of TAMs provides novel therapeutic opportunities to treat cancer. https://bit.ly/31OqHhe
Footnotes
Provenance: Commissioned article, peer reviewed
Conflict of interest: X. Zheng has nothing to disclose.
Conflict of interest: S. Mansouri has nothing to disclose.
Conflict of interest: A. Karger has nothing to disclose.
Conflict of interest: F. Grimminger has nothing to disclose.
Conflict of interest: W. Seeger has nothing to disclose.
Conflict of interest: S. Savai Pullamsetti has nothing to disclose.
Conflict of interest: C. Wheelock has nothing to disclose.
Conflict of interest: R. Savai has nothing to disclose.
Support statement: This work was supported by the Max Planck Society, Verein zur Förderung der Krebsforschung in Gieβen e.V., Von-Behring-Röntgen-Stiftung, a Rhön Klinikum AG grant, Institute for Lung Health (ILH), Cardio-Pulmonary Institute (CPI), the German Center for Lung Research (DZL). DFG, SFB CRC 1213 (Project A01, A05 to Pullamsetti SS and project A10* to Savai R), European Research Council (ERC) Consolidator Grant (#866051 to Pullamsetti SS) and Frankfurt Cancer Institute (LOEWE FCI).
- Received May 5, 2020.
- Accepted August 6, 2020.
- Copyright ©ERS 2020.
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.