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

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 striking enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared to 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. T cells treated with MNA stimulated secretion of the tumor promoting cytokine tumor necrosis factor alpha. Thus, TME-derived MNA contributes to the immune modulation of T cells and represents a promising immunotherapy target to treat human cancer.
Notes:
FSC files have been unmixed on SpectroFlo and do not require further compensation. Samples were run on two different days indicated by the date 28May2019 or 5June2019. The respective FMOs are indicated by the date for each experiment. The samples are labeled by the patient ID ie. "IROCXXX" and either AC for ascites or TB for tumor. FSC files for patient profiling (Figure 1, Figure S1 and Figure S2) contain the word "bulk" and are representative of the original patient sample. Samples post bead enrichment contain either "CD4+", "CD8+" or "CD45-" to indicate the enriched population. Original bulk and post bead enriched samples were analyzed at the same time. PDL1 was not analyzed due to overlap with viability dye.