The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers
Open accessAbstract
Immunotherapy may provide valid alternative therapy for patients with hormone-refractory metastatic prostate cancer. However, if the tumor environment exerts a suppressive action on antigen-specific tumor-infiltrating lymphocytes (TIL), immunotherapy will achieve little, if any, success. In this study, we analyzed the modulation of TIL responses by the tumor environment using collagen gel matrix–supported organ cultures of human prostate carcinomas. Our results indicate that human prostatic adenocarcinomas are infiltrated by terminally differentiated cytotoxic T lymphocytes that are, however, in an unresponsive status. We demonstrate the presence of high levels of nitrotyrosines in prostatic TIL, suggesting a local production of peroxynitrites. By inhibiting the activity of arginase and nitric oxide synthase, key enzymes of L-arginine metabolism that are highly expressed in malignant but not in normal prostates, reduced tyrosine nitration and restoration of TIL responsiveness to tumor were achieved. The metabolic control exerted by the tumor on TIL function was confirmed in a transgenic mouse prostate model, which exhibits similarities with human prostate cancer. These results identify a novel and dominant mechanism by which cancers induce immunosuppression in situ and suggest novel strategies for tumor immunotherapy.
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Cites
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Nitric oxide and the immune response
Bogdan, C. (2001) · Nature Immunology · doi:10.1038/ni1001-907 · Cited by 3,447
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Arginine metabolism: nitric oxide and beyond
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Proteomic method identifies proteins nitrated in vivo during inflammatory challenge
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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
The metabolic signature of macrophage responses
Viola, A., Munari, F., Sánchez-Rodríguez, R., Scolaro, T., & Castegna, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01462 · Cited by 2,021
Self-citationRegulation of immune responses by L-arginine metabolism
Bronte, V., & Zanovello, P. (2005) · Nature Reviews Immunology · doi:10.1038/nri1668 · Cited by 1,775
Self-citationSubsets of Myeloid-Derived Suppressor Cells in Tumor-Bearing Mice
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Kwon, E. D., Drake, C. G., Scher, H. I., Fizazi, K., Bossi, A., van den Eertwegh, A. J. M., Krainer, M., Houede, N., Santos, R., Mahammedi, H., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70189-5 · Cited by 1,511
Metadata
- Authors
- Bronte, V., Kasic, T., Gri, G., Gallana, K., Borsellino, G., Marigo, I., Battistini, L., Iafrate, M., Prayer-Galetti, T., Pagano, F., & Viola, A.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-04-11
- Volume
- 201
- Issue
- 8
- Pages
- 1257-1268
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2154339682
- Cited by
- 396
- References
- 10
- FWCI
- 8.37
- Type
- journal article
- Language
- en
- Open access
- green
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- Bronte, V., Kasic, T., Gri, G., Gallana, K., Borsellino, G., Marigo, I., Battistini, L., Iafrate, M., Prayer-Galetti, T., Pagano, F., & Viola, A. (2005). Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20042028
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