The Tumor Metabolite 5′-Deoxy-5′Methylthioadenosine (MTA) Inhibits Maturation and T Cell-Stimulating Capacity of Dendritic Cells

Brummer C, Singer K, Henrich F, Peter K, Strobl C, Neueder B, Bruss C, Renner K, Pukrop T, Herr W, Aigner M, Kreutz M (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Cells MDPI

Book Volume: 13

Article Number: 2114

Journal Issue: 24

DOI: 10.3390/cells13242114

Abstract

Metabolite accumulation in the tumor microenvironment fosters immune evasion and limits the efficiency of immunotherapeutic approaches. Methylthioadenosine phosphorylase (MTAP), which catalyzes the degradation of 5′-deoxy-5′methylthioadenosine (MTA), is downregulated in many cancer entities. Consequently, MTA accumulates in the microenvironment of MTAP-deficient tumors, where it is known to inhibit tumor-infiltrating T cells and NK cells. However, the impact of MTA on other intra-tumoral immune cells has not yet been fully elucidated. To study the effects of MTA on dendritic cells (DCs), human monocytes were maturated into DCs with (MTA-DC) or without MTA (co-DC) and analyzed for activation, differentiation, and T cell-stimulating capacity. MTA altered the cytokine secretion profile of monocytes and impaired their maturation into dendritic cells. MTA-DCs produced less IL-12 and showed a more immature-like phenotype characterized by decreased expression of the co-stimulatory molecules CD80, CD83, and CD86 and increased expression of the monocyte markers CD14 and CD16. Consequently, MTA reduced the capability of DCs to stimulate T cells. Mechanistically, the MTA-induced effects on monocytes and DCs were mediated by a mechanism beyond adenosine receptor signaling. These results provide new insights into how altered polyamine metabolism impairs the maturation of monocyte-derived DCs and impacts the crosstalk between T and dendritic cells.

Involved external institutions

Bayerisches Zentrum für Krebsforschung (BZKF) DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE)

How to cite

APA:

Brummer, C., Singer, K., Henrich, F., Peter, K., Strobl, C., Neueder, B.,... Kreutz, M. (2024). The Tumor Metabolite 5′-Deoxy-5′Methylthioadenosine (MTA) Inhibits Maturation and T Cell-Stimulating Capacity of Dendritic Cells. Cells, 13(24). https://doi.org/10.3390/cells13242114

MLA:

Brummer, Christina, et al. "The Tumor Metabolite 5′-Deoxy-5′Methylthioadenosine (MTA) Inhibits Maturation and T Cell-Stimulating Capacity of Dendritic Cells." Cells 13.24 (2024).

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