期刊
CANCER RESEARCH
卷 79, 期 8, 页码 1938-1951出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-18-1544
关键词
-
类别
资金
- Associazione Italiana Ricerca sul Cancro (AIRC) Program Innovative Tools for Cancer Risk Assessment and Diagnosis, 5 per mille [12162, 14194, 15585, 19885]
- AIRC, fellowship Pierluigi Meneghelli [19682]
- Leonino Fontana e Maria Lionello Fellowship [14832]
- SIF-Takeda grant in Pharmaceutical oncology
- Fondazione Veronesi Fellowship 2018
- Fondazione San Paolo, Dipartimento di Scienze del Farmaco, Universita del Piemonte Orientale, Novara
- Fondazione Cariplo
- Ministero Universita Ricerca (MIUR)
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 HIF1 alpha-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据