Metabolic changes in tumor cells and tumor-associated macrophages: A mutual relationship

Abstract

In order to adapt to the reduced availability of nutrients and oxygen in the tumor microenvironment and the increased requirements of energy and building blocks necessary for maintaining their high proliferation rate, malignant cells undergo metabolic changes that result in an increased production of lactate, nitric oxide, reactive oxygen species, prostaglandins and other byproducts of arachidonic acid metabolism that influence both the composition of the inflammatory microenvironment and the function of the tumor-associated macrophages (TAMs). In response to cues present in the TME, among which products of altered tumor cell metabolism, TAMs are also required to reprogram their metabolism, with activation of glycolysis, fatty acid synthesis and altered nitrogen cycle metabolism. These changes result in functional reprogramming of TAMs which includes changes in the production of cytokines and angiogenetic factors, and contribute to the tumor progression and metastasis. Understanding the metabolic changes governing the intricate relationship between the tumor cells and the TAMs represents an essential step towards developing novel therapeutic approaches targeting the metabolic reprogramming of the immune cells to potentiate their tumoricidal potential and to circumvent therapy resistance.

Designing Stimuli‐Responsive Upconversion Nanoparticles that Exploit the Tumor Microenvironment

“…Autocrine and paracrine signaling within the TME leads to stiffening of the extracellular matrix, increased interstitial fluid pressure, blood and lymph vessel formation, the development of necrotic regions, and ultimately metastasis. [ 17 ] In terms of novel therapeutic design, understanding of the TME composition, along with any specific changes in it during tumor development, is important. Additionally, characterizations of the vascular abnormalities, oxygenation, perfusion, pH, and metabolic states of the TME, along with cancer pathophysiology, are vital for tailoring the TME‐targeted nanomedicines.…”

Translating In Vitro T Cell Metabolic Findings to In Vivo Tumor Models of Nutrient Competition

“…Furthermore, any attempts to modulate metabolism in the tumor microenvironment is likely going to cascade and affect many of the surrounding cells and may have cell-specific effects. For example, enhancing tumor glycolysis is sufficient to decrease available glucose for T cells, but may also create a better environment for tumor associated macrophages and T regulatory cells (Angelin et al, 2017; Chang et al, 2015; Netea-Maier et al, 2018). In addition, simply increasing T cell activity is sufficient to modulate metabolites in the serum of mice, and the effects of these changes on other cell types is not understood (Miyajima et al, 2017).…”

Autofluorescence imaging of 3D tumor-macrophage microscale cultures resolves spatial and temporal dynamics of macrophage metabolism

“…Cell function has been correlated with metabolism across numerous cell types, including macrophages 13 . Therefore, monitoring metabolic preferences within macrophages could reveal heterogeneity in macrophage phenotype and function.…”