Our results showed that Piezo1 responds to inflammatory stimulation or stiffness signals, and subsequently, Piezo1 effectively integrates metabolism signals and ion signals pathway including SIRT1-HIF1α-glycolysis and the calcium-calcineurin-NFAT signaling pathway to direct the differentiation of Treg and TH1 cells by regulating the production of DC-derived polarizing cytokines, including IL-12 and TGFβ1, in the context of tumor microenvironment (Figure 7—figure supplement 1). Here, TGFB1 is linked to neoplasm.