The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function
Open accessAbstract
Phosphodiesterase-5 (PDE5) inhibitors (sildenafil, tadalafil, and vardenafil) are agents currently in clinical use for nonmalignant conditions. We report the use of PDE5 inhibitors as modulators of the antitumor immune response. In several mouse tumor models, PDE5 inhibition reverses tumor-induced immunosuppressive mechanisms and enables a measurable antitumor immune response to be generated that substantially delays tumor progression. In particular, sildenafil, down-regulates arginase 1 and nitric oxide synthase–2 expression, thereby reducing the suppressive machinery of CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSCs) recruited by growing tumors. By removing these tumor escape mechanisms, sildenafil enhances intratumoral T cell infiltration and activation, reduces tumor outgrowth, and improves the antitumor efficacy of adoptive T cell therapy. Sildenafil also restores in vitro T cell proliferation of peripheral blood mononuclear cells from multiple myeloma and head and neck cancer patients. In light of the recent data that enzymes mediating MDSC-dependent immunosuppression in mice are active also in humans, these findings demonstrate a potentially novel use of PDE5 inhibitors as adjuncts to tumor-specific immune therapy.
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Intratumoral T Cells, Recurrence, and Survival in Epithelial Ovarian Cancer
Zhang, L., Conejo-Garcia, J. R., Katsaros, D., Gimotty, P. A., Massobrio, M., Regnani, G., Makrigiannakis, A., Gray, H., Schlienger, K., Liebman, M. N., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa020177 · Cited by 3,397
Demonstration of an interferon γ-dependent tumor surveillance system in immunocompetent mice
Kaplan, D. H., Shankaran, V., Dighe, A. S., Stockert, E., Aguet, M., Old, L. J., & Schreiber, R. D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7556 · Cited by 1,465
Rodriguez, P. C., Quiceno, D. G., Zabaleta, J., Ortiz, B., Zea, A. H., Piazuelo, M. B., Delgado, A., Correa, P., Brayer, J., Sotomayor, E. M., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0465 · Cited by 1,276
Yang, L., DeBusk, L. M., Fukuda, K., Fingleton, B., Green-Jarvis, B., Shyr, Y., Matrisian, L. M., Carbone, D. P., & Lin, P. C. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.08.031 · Cited by 1,140
Cited by
Myeloid-derived-suppressor cells as regulators of the immune system
Gabrilovich, D. I., & Nagaraj, S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2506 · Cited by 6,753
Coordinated regulation of myeloid cells by tumours
Gabrilovich, D. I., Ostrand-Rosenberg, S., & Bronte, V. (2012) · Nature Reviews Immunology · doi:10.1038/nri3175 · Cited by 3,544
Self-citationTumor microenvironment and therapeutic response
Wu, T., & Dai, Y. (2017) · Cancer Letters · doi:10.1016/j.canlet.2016.01.043 · Cited by 1,802
Vincent, J., Mignot, G., Chalmin, F., Ladoire, S., Bruchard, M., Chevriaux, A., Martin, F., Apetoh, L., Rébé, C., & Ghiringhelli, F. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-3690 · Cited by 1,245
Altered macrophage differentiation and immune dysfunction in tumor development
Sica, A., & Bronte, V. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31422 · Cited by 1,238
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Metadata
- Authors
- Serafini, P., Meckel, K., Kelso, M., Noonan, K., Califano, J., Koch, W., Dolcetti, L., Bronte, V., & Borrello, I.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2006-11-13
- Volume
- 203
- Issue
- 12
- Pages
- 2691-2702
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2120539661
- Cited by
- 766
- References
- 4
- FWCI
- 8.24
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Serafini, P., Meckel, K., Kelso, M., Noonan, K., Califano, J., Koch, W., Dolcetti, L., Bronte, V., & Borrello, I. (2006). Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20061104
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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