NNMT and cancer: More recently, nicotinamide N-methyltransferase (NNMT) positive fibroblasts have been shown to mediate recruitment and differentiation of suppressive macrophages in human and mouse BLCA.57 Of note, cancer cells and macrophages stablish metabolic circuitries that may dictate the co-evolution of both cell types in later stages,58 therefore detached from CAFs, as it is the case for serine metabolism in BLCA.59 These observations reflect the dynamic nature of the TME as BLCA progresses, likely influenced by cancer cell intrinsic characteristics since it appears tied to tumor progression.