1-Methylnicotinamide is an Immune Regulatory Metabolite in Human Ovarian Cancer

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2021 Feb 1

PMID 33523930

Citations 33

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

Affiliations

Soon will be listed here.

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 -methyltransferase, the enzyme that catalyzes the transfer of a methyl group from -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.

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