American Association for Cancer Research
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00085472can181544-sup-202103_2_supp_5305387_plzl9c.pdf (423.88 kB)

Figure S2 from Nicotinamide Phosphoribosyltransferase Acts as a Metabolic Gate for Mobilization of Myeloid-Derived Suppressor Cells

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posted on 2023-03-31, 03:08 authored by Cristina Travelli, Francesca Maria Consonni, Sabina Sangaletti, Mariangela Storto, Sara Morlacchi, Ambra A. Grolla, Ubaldina Galli, Gian Cesare Tron, Paola Portararo, Lorenza Rimassa, Tiziana Pressiani, Massimiliano Mazzone, Rosalinda Trovato, Stefano Ugel, Vincenzo Bronte, Claudio Tripodo, Mario P. Colombo, Armando A. Genazzani, Antonio Sica

NAMPT levels in conditional-deficient mice

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Associazione Italiana Ricerca sulCancro

Leonino Fontana e Maria Lionello Fellowship

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ARTICLE ABSTRACT

Cancer induces alteration of hematopoiesis to fuel disease progression. We report that in tumor-bearing mice the macrophage colony-stimulating factor elevates the myeloid cell levels of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD salvage pathway, which acts as negative regulator of the CXCR4 retention axis of hematopoietic cells in the bone marrow. NAMPT inhibits CXCR4 through a NAD/Sirtuin 1–mediated inactivation of HIF1α-driven CXCR4 gene transcription, leading to mobilization of immature myeloid-derived suppressor cells (MDSC) and enhancing their production of suppressive nitric oxide. Pharmacologic inhibition or myeloid-specific ablation of NAMPT prevented MDSC mobilization, reactivated specific antitumor immunity, and enhanced the antitumor activity of immune checkpoint inhibitors. Our findings identify NAMPT as a metabolic gate of MDSC precursor function, providing new opportunities to reverse tumor immunosuppression and to restore clinical efficacy of immunotherapy in patients with cancer. These findings identify NAMPT as a metabolic gate of MDSC precursor function, providing new opportunities to reverse tumor immunosuppression and to restore clinical efficacy of immunotherapy in cancer patients.

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    Cancer Research

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    Keywords

    ImmunologyImmune responses to cancerImmunotherapyCellular immunotherapySarcomas

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    CC BY

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