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These endogenous clocks impose temporal gating across a range of functions, such as phagocytosis, cytokine/chemokine production, and antibacterial and antiviral activity 53

Furthermore, several preclinical studies have shown that metformin in combination with PD-1 inhibitors inhibits the growth of cancer cells in mouse models of different tumor types and leads to a significant increase in the number of tumor-infiltrating CD8 + T cells [397, 398]