1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer

Sci Adv. 2021 Jan 20;7(4):eabe1174. doi: 10.1126/sciadv.abe1174. Print 2021 Jan.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Ascites* / pathology
  • Female
  • Humans
  • Niacinamide / analogs & derivatives
  • Niacinamide / pharmacology
  • Ovarian Neoplasms* / metabolism
  • Tumor Microenvironment

Substances

  • Niacinamide
  • N(1)-methylnicotinamide