Metabolic programming of tumor associated macrophages in the context of cancer treatment

Abstract

Tumor associated macrophages (TAMs) are important components of the tumor microenvironment (TME). They are characterized by a remarkable functional plasticity, thereby mostly promoting cancer progression. Changes in immune cell metabolism are paramount for this functional adaptation. Here, we review the functional consequences of the metabolic programming of TAMs and the influence of local and systemic targeted therapies on the metabolic characteristics of the TME that shape the functional phenotype of the TAMs. Understanding these metabolic changes within the context of the cross-talk between the different components of the TME including the TAMs and the tumor cells is an essential step that can pave the way towards identifications of ways to improve responses to different treatments, to overcome resistance to treatments, tumor progression and reduce treatment-specific toxicity.

Macrophage diversity in cancer revisited in the era of single-cell omics

“…The complex metabolic circuitries between TAMs and tumor cells and the TME have recently been reviewed extensively [76,77]. Notably, TAM clusters feature various metabolic patterns, as inferred from scRNA-seq data through pathway analysis.…”

Perspective Chapter: Impact of Tumor Metabolism on Immune Cells in the Tumor Microenvironment

“…Tumor-associated macrophages (TAMs) are macrophages that are specifically recruited into tumor tissue due to cytokines and growth factors secreted by cells within the tumor microenvironment [43]. TAMs are one of the most abundant leukocytes within the TME and have been implicated in tumor progression and metastasis [44]. Macrophages were further classified as inactive (M0), pro-inflammatory (M1), and anti-inflammatory (M2) subtypes based on specific immune responses elicited by these cells.…”

The Role of the BH4 Cofactor in Nitric Oxide Synthase Activity and Cancer Progression: Two Sides of the Same Coin

“…Important components of the TME in various types of cancer, TAMs exhibit a wide spectrum of phenotypic and functional profiles regulated by different signals of the surrounding environment [130,131]. Therefore, functional reprogramming of TAMs to a more anti-tumorigenic profile has been explored as presenting a therapeutic potential [132,133]. CA1d human breast cancer cells and M2 macrophages treated with sepiapterin produced higher levels of NO than polyamines.…”