1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer
Menée à partir de l'analyse de lymphocytes T provenant de tumeurs et d'ascites de patientes atteintes d'un carcinome séreux de l'ovaire de haut-grade, cette étude met en évidence un mécanisme par lequel le 1-méthyl-nicotinamide du microenvironnement tumoral induit la sécrétion de TNFalpha par les lymphocytes T
Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few exceptions, their identities remain largely unknown. Here, we profiled tumor and T cells from tumor and ascites of patients with high-grade serous carcinoma (HGSC) to uncover the metabolomes of these distinct TME compartments. Cells within the ascites and tumor had pervasive metabolite differences, with a notable enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared with ascites. Despite the elevated levels of MNA in T cells, the expression of nicotinamide N-methyltransferase, the enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine to nicotinamide, was restricted to fibroblasts and tumor cells. Functionally, MNA induces T cells to secrete the tumor-promoting cytokine tumor necrosis factor alpha. Thus, TME-derived MNA contributes to the immune modulation of T cells and represents a potential immunotherapy target to treat human cancer.