Automated Organization ProfileHuman Pathology Section, Department of Health Sciences, University of Palermo, Palermo, Italy. AND Tumor and Microenvironment Histopathology Unit, the FIRC Institute of Molecular Medicine (IFOM), Milan, Italy.
Human Pathology Section, Department of Health Sciences, University of Palermo, Palermo, Italy. AND Tumor and Microenvironment Histopathology Unit, the FIRC Institute of Molecular Medicine (IFOM), Milan, Italy.
Current S-Index
Sum of Dataset Indices for all datasets
Average Dataset Index per Dataset
Average Dataset Index per dataset
Total Datasets
Total datasets in this organization
Average FAIR Score
Average FAIR Score per dataset
Total Citations
Total citations to the organization's datasets
Total Mentions
Total mentions of the organization's datasets
S-Index Interpretation
The S-Index (Sharing Index) is a comprehensive metric that represents the cumulative impact of all your datasets. It is calculated as the sum of Dataset Index scores across all your claimed datasets.
What it means:
- A higher S-index indicates greater overall impact of your datasets relative to typical datasets in their fields of research
- The S-Index grows as you add more datasets or as existing datasets gain more citations and mentions
- It provides a single number to track your research data impact over time
Current S-Index: 3.7 (sum of 2 datasets Dataset Index scores)
More information here.
S-Index Over Time
Cumulative Citations Over Time
Cumulative Mentions Over Time
Datasets
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. SIGNIFICANCE: 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.
Authors
- Travelli C ;
- Consonni FM ;
- Sangaletti S ;
- Storto M ;
- Morlacchi S ;
- Grolla AA ;
- Galli U ;
- GC, Tron ;
- Portararo P ;
- L, Rimassa ;
- Pressiani T ;
- Mazzone M ;
- Trovato R ;
- Ugel S ;
- V, Bronte ;
- Tripodo C ;
- MP, Colombo ;
- Genazzani AA ;
- Sica A
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. SIGNIFICANCE: 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.
Authors
- Travelli C ;
- Consonni FM ;
- Sangaletti S ;
- Storto M ;
- Morlacchi S ;
- Grolla AA ;
- Galli U ;
- GC, Tron ;
- Portararo P ;
- L, Rimassa ;
- Pressiani T ;
- Mazzone M ;
- Trovato R ;
- Ugel S ;
- V, Bronte ;
- Tripodo C ;
- MP, Colombo ;
- Genazzani AA ;
- Sica A