Fig. 1

NAD + metabolism and TIME. A NAD + is synthesized by three pathways: Kynurenine pathway, Preiss-Handler pathway, and salvage pathway. Under the action of key synthetases such as NAMPT and consuming enzymes such as sirtuins, PARP, and CD38, NAD⁺ is continuously synthesized and consumed, which generates a large amount of ATP for the maintenance of cell life activities. B The cells in the tumor immune microenvironment mainly include anti-tumor cells and pro-tumor cells. The former mainly include cytotoxic T cells (CTLs), NK cells, dendritic cells (DC), M1 macrophages, and N1 neutrophils. The latter mainly includes M2 macrophages, bone marrow-derived inhibitory cells (MDSC) and regulatory T cells (Treg). These cells influence tumors through a variety of signaling pathways and cytokines