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Piezo1 was originally identified as a mechanically activated, nonselective cation ion channel, with significant permeability to calcium ions, is evolutionally conserved, and is involved in the proliferation and development of various types of cells, in the context of various types of mechanical or innate stimuli. Recently, our study and work by others have reported that Piezo1 from all kinds of immune cells is involved in regulating many diseases, including infectious inflammation and cancer. This review summarizes the recent progress made in understanding the immunoregulatory role and mechanisms of the mechanical receptor Piezo1 in inflammation and cancer and provides new insight into the biological significance of Piezo1 in regulating immunity and tumors. [ABSTRACT FROM AUTHOR]

Summary: Follicular T helper (TFH) cells are specialized T cells that support B cells, which are essential for humoral immunity. TFH cells express the transcription factor B‐cell lymphoma 6 (Bcl‐6), chemokine (C‐X‐C motif) receptor (CXCR) 5, the surface receptors programmed cell death protein 1 (PD‐1) and inducible T‐cell costimulator (ICOS), the cytokine IL‐21 and other molecules. The activation, proliferation and differentiation of TFH cells are closely related to dynamic changes in cellular metabolism. In this review, we summarize the progress made in understanding the development and functional differentiation of TFH cells. Specifically, we focus on the regulatory mechanisms of TFH cell functional differentiation, including regulatory signalling pathways and the metabolic regulatory mechanisms of TFH cells. In addition, TFH cells are closely related to immune‐associated diseases, including infections, autoimmune diseases and cancers. [ABSTRACT FROM AUTHOR]

Macrophages differentiated into a classically activated (M1) or alternatively activated phenotype (M2) in infection and tumor, but the precise effects of glycolysis and oxidative phosphorylation (OXPHOS) metabolic pathway remain unclear. Herein, the effects of glycolysis or OXPHOS on macrophage polarizations were investigated using a pharmacological approach in mice. 2-Deoxy-D-glucose (2-DG) treatments, which blocks the key enzyme hexokinase of glycolysis, efficiently inhibits a specific switch to M1 lineage, decreasing the secretion of pro-inflammatory cytokines and expressions of co-stimulatory molecules associated with relieving infectious inflammation in vitro and in vivo. Glycolytic activation through the hypoxia-inducible factor-1α (HIF-1α) pathway was required for differentiation to the M1 phenotype, which conferred protection against infection. Dimethyl malonate (DMM) treatment, which blocks the key element succinate of OXPHOS, efficiently inhibits a specific switch to M2 lineage when macrophages receiving M2 stimulation, decreasing the secretion of anti-inflammatory cytokine and CD206 expressions. Mitochondrial dynamic alterations including mitochondrial mass, mitochondrial membrane potential (Dym) and ROS productions were critically for differentiation to the M2 phenotype, which conferred protection against anti-tumor immunity. Glycolysis is also required for macrophage M2 differentiation. Thus, these data provide a basis for a comprehensively understanding the role of glycolysis and OXPHOS in macrophage differentiation during anti-infection and anti-tumor inflammation. [ABSTRACT FROM AUTHOR]

Simple Summary: Myeloid-Derived Suppressor Cells (MDSCs) have been regarded as the main promoters of cancer development in recent years. They can protect tumor cells from being eliminated by neutralizing the anti-tumor response mediated by T cells, macrophages and dendritic cells (DCs). Therefore, different treatment methods targeting MDSCs, including chemotherapy, radiotherapy and immunotherapy, have been developed and proven to effectively inhibit tumor expansion. Herein, we summarize the immunosuppressive role of MDSCs in the tumor microenvironment and some effective treatments targeting MDSCs, and discuss the differences between different therapies. Myeloid-derived suppressor cells (MDSCs), which are activated under pathological conditions, are a group of heterogeneous immature myeloid cells. MDSCs have potent capacities to support tumor growth via inhibition of the antitumoral immune response and/or the induction of immunosuppressive cells. In addition, multiple studies have demonstrated that MDSCs provide potential therapeutic targets for the elimination of immunosuppressive functions and the inhibition of tumor growth. The combination of targeting MDSCs and other therapeutic approaches has also demonstrated powerful antitumor effects. In this review, we summarize the characteristics of MDSCs in the tumor microenvironment (TME) and current strategies of cancer treatment by targeting MDSCs. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) are a group of immunosuppressive cells that play crucial roles in promoting tumor growth and protecting tumors from immune recognition in tumor-bearing mice and cancer patients. Recently, it has been shown that the metabolic activity of MDSCs plays an important role in the regulation of their inhibitory function, especially in the processes of tumor occurrence and development. The MDSC metabolism, such as glycolysis, fatty acid oxidation and amino acid metabolism, is rewired in the tumor microenvironment (TME), which enhances the immunosuppressive activity, resulting in effector T cell apoptosis and suppressive cell proliferation. Herein, we summarized the recent progress in the metabolic reprogramming and immunosuppressive function of MDSCs during tumorigenesis. [ABSTRACT FROM AUTHOR]