The Journal of Experimental Medicine
PBL InterferonSource
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 11 April 2005 doi:10.1084/jem.20042028
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 8, 1257-1268
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2539K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bronte, V.
Right arrow Articles by Viola, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bronte, V.
Right arrow Articles by Viola, A.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*(L)-ARGININE
*L-TYROSINE
Medline Plus Health Information
*Prostate Cancer
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers

Vincenzo Bronte1, Tihana Kasic4, Giorgia Gri4, Keti Gallana4, Giovanna Borsellino5, Ilaria Marigo1, Luca Battistini5, Massimo Iafrate2, Tommaso Prayer-Galetti2, Francesco Pagano2,4, and Antonella Viola3,4

1 Department of Oncology and Surgical Sciences, University of Padova
2 Department of Urology, University of Padova
3 Department of Biomedical Sciences, University of Padova
4 Venetian Institute of Molecular Medicine, 35100 Padova, Italy
5 Neuroimmunology Unit, Santa Lucia Foundation Scientific Institute IRCCS, 00143 Rome, Italy

CORRESPONDENCE Antonella Viola: antonella.viola{at}unipd.it

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.

Abbreviations used: ARG, arginase; L-Arg, L-arginine; L-NMMA, N-monomethyl- L-arginine; NO, nitric oxide; NOHA, N-hydroxy-L-arginine; NOS, nitric oxide synthase; PCa, prostate carcinoma; TIA-1, T cell intracellular antigen 1; TIL, tumor-infiltrating lymphocytes; TRAMP, transgenic adenocarcinoma mouse prostate.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

Prostate cancer's one-two punch
Heather L. Van Epps
J. Exp. Med. 2005 201: 1180-1181. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS