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

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.

• Authors: Marisa K Kilgour, Sarah MacPherson, Lauren G Zacharias, Abigail E Ellis, Ryan D Sheldon, Elaine Y Liu, Sarah Keyes, Brenna Pauly, Gillian Carleton, Bertrand Allard, Julian Smazynski, Kelsey S Williams, Peter H Watson, John Stagg, Brad H Nelson, Ralph J DeBerardinis, Russell G Jones, Phineas T Hamilton, Julian J Lum
• Journal: Science advances (Sci Adv) Vol. 7 Issue 4 (01 2021) ISSN: 2375-2548 [Electronic] United States
• PMID: 33523930 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Chemical References

• Niacinamide
• N(1)-methylnicotinamide

Topics

• Ascites (pathology)
• Female
• Humans
• Niacinamide (analogs & derivatives, pharmacology)
• Ovarian Neoplasms (metabolism)
• Tumor Microenvironment