[Cholesterol Metabolism and Tumor Immunity].

Cholesterol, an important lipid molecule of organisms, is involved in the formation of cell membrane structure, bile acid metabolism and steroid hormone synthesis, playing an important role in the regulation of cell structure and functions. In recent years, a large number of studies have shown that cholesterol metabolism is reprogrammed during tumor formation and development. In addition to directly affecting the biological behavior of tumor cells, cholesterol metabolic reprogramming also regulates the antitumor activity of immune cells in the tumor microenvironment. We reviewed herein the cholesterol metabolism reprogramming of and interactions among immune cells including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), dendritic cells (DCs), and T cells in the tumor microenvironment. However, the relationship between cholesterol metabolism and tumor immunity in tumor microenvironment is complex and diversified. The differences and similarities of cholesterol metabolism reprogramming in tumor microenvironment in regulating immune cell activity and the specific regulatory mechanism are still unresolved issues. Targeted intervention of the cholesterol metabolism pathway of immune cells is expected to become a new strategy of cholesterol metabolism in tumor immunotherapy.

[A Review of the Lipid Metabolism Reprogramming in Tumor Associated Macrophages].

Tumor associated macrophages (TAMs) are one of the most common types of stromal cells in solid tumors. They are closely related to the immunosuppressive status of tumor microenvironment and potentiate the malignant progress of tumors. Studies have shown that metabolism in tumor associated macrophages has been reprogrammed and involved in the regulation of their own polarization and corresponding functions and phenotypes. Metabolic reprogramming refers to the alteration of key enzymes activity, substrate and its associated metabolites' concentration in a certain metabolic pathway, which accounts for the disorder of original metabolic states. In this paper, we mainly concentrated on the lipid metabolic reprogramming of TAMs, including triglycerides, fatty acids and their derivatives, cholesterol, phospholipids, and their regulations on tumor progression. However, the metabolism of tumor and tumor microenvironment cells is highly heterogeneous. It is worthy of further exploration on the similarities and differences of lipid metabolism reprogramming between stromal cells and tumor cells, and the mechanism of how reprogramming modulates cell activity. It will be a new strategy for immunotherapy of tumor with metabolic intervention to accurately target the lipid metabolism reprogramming of TAMs, so as to promote the polarization of TAMs to M1 like macrophages, when synthetically considering the diverse types of tumors and different stages of development.

Exercise-induced Musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis.

The effects of exercise on fibro-adipogenic progenitors (FAPs) are unclear, and the direct molecular link is still unknown. In this study, we reveal that exercise reduces the frequency of FAPs and attenuates collagen deposition and adipose formation in injured or disused muscles through Musclin. Mechanistically, Musclin inhibits FAP proliferation and promotes apoptosis in FAPs by upregulating FILIP1L. Chromatin immunoprecipitation (ChIP)-qPCR confirms that FoxO3a is the transcription factor of FILIP1L. In addition, the Musclin/FILIP1L pathway facilitates the phagocytosis of apoptotic FAPs by macrophages through downregulating the expression of CD47. Genetic ablation of FILIP1L in FAPs abolishes the effects of exercise or Musclin on FAPs and the benefits on the reduction of fibrosis and fatty infiltration. Overall, exercise forms a microenvironment of myokines in muscle and prevents the abnormal accumulation of FAPs in a Musclin/FILIP1L-dependent manner. The administration of exogenous Musclin exerts a therapeutic effect, demonstrating a potential therapeutic approach for muscle atrophy or acute muscle injury.