Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Abstract

Macrophages are key innate immune cells in the tumor microenvironment (TME) that regulate primary tumor growth, vascularization, metastatic spread and tumor response to various types of therapies. The present review highlights the mechanisms of macrophage programming in tumor microenvironments that act on the transcriptional, epigenetic and metabolic levels. We summarize the latest knowledge on the types of transcriptional factors and epigenetic enzymes that control the direction of macrophage functional polarization and their pro- and anti-tumor activities. We also focus on the major types of metabolic programs of macrophages (glycolysis and fatty acid oxidation), and their interaction with cancer cells and complex TME. We have discussed how the regulation of macrophage polarization on the transcriptional, epigenetic and metabolic levels can be used for the efficient therapeutic manipulation of macrophage functions in cancer.

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

“…Tumor-associated macrophages (TAMs) are key innate immune cells in tumor microenvironment (TME) that regulate growth of primary tumors, antitumor adaptive immune response, tumor angiogenesis, extracellular matrix remodeling, intravasation in the vasculature, extravasation in metastatic sites; they establish beneficial conditions for metastatic cells in the secondary organs, and interact with various types of therapies (1,2). Signaling, epigenetic and metabolic mechanisms cooperate to form functional TAM phenotypes (3).…”

Glycolytic and immunological alterations in human U937 monocytes in response to H1N1 infection

“…Based on the initial stimuli, either of infectious or noninfectious origin, monocytes differentiate into macrophages that are used to be classified into two main classes known as M1 and M2, which express different functional programs in response to microenvironmental signals. 3,32 However, classical versus alternative macrophage activation definition is not perfect to genuinely describe F I G U R E 5 Differential expression of PFKs mRNA in the lysates of uninfected or H1N1 infected U937 cells by qRT-PCR. 10 6 U937 cells were cultured in six-well plates and stimulated with 100 μl/ml supernatant of U937 cells previously exposed to H1N1 virus (UI H1N1 U937) or 100 ng/ml PMA (UI PMA U937) for 24 hr or not stimulated (UI U937) then infected with H1N1 (0.1 MOI) for 12-24-36 hr (I H1N1 U937, I PMA U937, and I U937).…”

A Sonosensitizer-based Polymeric Nanoplatform for Realizing Chemo-sonodynamic Combination Therapy of Lung Cancer 

“…Considering the RTV and H&E staining results for 'R' and 'L' tumors, it was speculated that the immune system of mice might be activated during the course of administration after SDT treatment. Thus, the serum composition of IL-10 and IL-12 was measured by Elisa kit aiming at evaluating the generation of M2 and M1 subtypes of macrophages that acted as the pro/anti-in ammatory cytokines after different treatment [36]. Results suggested that the IL-10 content decreased after SDT treatment with C-NPs or DTX/C-NPs, however the variation was on the opposite side for the IL-12 factor (Fig.…”