Abstract:
: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.
journal_name
Sci Advjournal_title
Science advancesauthors
Kilgour MK,MacPherson S,Zacharias LG,Ellis AE,Sheldon RD,Liu EY,Keyes S,Pauly B,Carleton G,Allard B,Smazynski J,Williams KS,Watson PH,Stagg J,Nelson BH,DeBerardinis RJ,Jones RG,Hamilton PT,Lum JJdoi
10.1126/sciadv.abe1174subject
Has Abstractpub_date
2021-01-20 00:00:00issue
4issn
2375-2548pii
7/4/eabe1174journal_volume
7pub_type
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