Glycolysis regulation in tumor‐associated macrophages: Its role in tumor development and cancer treatment

Abstract

Tumor‐associated macrophages constitute the main cell population in the tumor microenvironment and play a crucial role in regulating the microenvironment composition. Emerging evidence has revealed that the metabolic profile determines the tumor‐associated macrophage phenotype. Tumor‐associated macrophage function is highly dependent on glucose metabolism, with glycolysis being the major metabolic pathway. Recent reports have demonstrated diversity in glucose flux of tumor‐associated macrophages and complex substance communication with cancer cells. However, how the glucose flux in tumor‐associated macrophages connects with glycolysis to influence tumor progression and the tumor microenvironment is still obscure. Moreover, while the development of single‐cell sequencing technology allows a clearer and more accurate classification of tumor‐associated macrophages, the metabolic profiles of tumor‐associated macrophages from the perspective of single‐cell omics has not been well summarized. Here, we review the current state of knowledge on glucose metabolism in tumor‐associated macrophages and summarize the metabolic profiles of different tumor‐associated macrophage subtypes from the perspective of single‐cell omics. Additionally, we describe the current strategies targeting glycolysis in tumor‐associated macrophages for cancer therapy.

Single-cell and spatial transcriptomics reveal a high glycolysis B cell and tumor-associated macrophages cluster correlated with poor prognosis and exhausted immune microenvironment in diffuse large B-cell lymphoma

“…4 B. Based on previous literature classifications [ 54 – 58 ] of macrophages, monocytes, and dendritic cells, we categorized five cell types using specific markers as monocytes (FCN1 + S100A8 + APOBEC3A + ), dendritic cells_1 (CLEC10A + CD1C + CD1E + ), lipid-associated tumor-associated macrophages (LA_TAMs) (APOC1 + APOE + ACP5 + CCL18 + ), interferon-primed_TAMs (IFN_TAMs) (PD-L1 + PD-L2 + CXCL10 + ), and dendritic cells 2 (CLEC9A + THBD + ). Enhanced TF activities for RELA, NFKB1, and HIF1A (known as glycolytic promoting factors) were specifically observed in IFN_TAMs (Fig.…”