HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Walker, P. R. Articles by Dietrich, P.-Y. Search for Related Content PubMed PubMed Citation Articles by Walker, P. R. Articles by Dietrich, P.-Y. Pubmed/NCBI databases Medline Plus Health Information Brain Cancer

The Brain Parenchyma Is Permissive for Full Antitumor CTL Effector Function, Even in the Absence of CD4 T Cells¹

Paul R. Walker^2,*,, Thomas Calzascia^*, Valérie Schnuriger^*, Nathalie Scamuffa^*, Philippe Saas, Nicolas de Tribolet and Pierre-Yves Dietrich^*

^* Laboratory of Tumor Immunology, Division of Oncology, and Department of Neurosurgery, University Hospital Geneva, Geneva, Switzerland; and Laboratory of Immunology, E.F.S. Bourgogne Franche Comté, Besançon, France

Effective antitumor immune responses against cerebral malignancies have been demonstrated in several models, but precise cellular function of specific effector cells is poorly understood. We have explored this topic by analyzing the MHC class I-restricted T cell response elicited after implantation of HLA-CW3-transfected P815 mastocytoma cells (P815-CW3) in syngeneic mice. In this model, tumor-specific CTLs use a distinctive repertoire of TCRs that allows ex vivo assessment of the response by immunophenotyping and TCR spectratyping. Thus, for the first time in a brain tumor model, we are able to directly visualize ex vivo CTLs specific for a tumor-expressed Ag. Tumor-specific CTLs are detected in the CNS after intracerebral implantation of P815-CW3, together with other inflammatory cells. Moreover, despite observations in other models suggesting that CTLs infiltrating the brain may be functionally compromised and highly dependent upon CD4 T cells, in this syngeneic P815-CW3 model, intracerebral tumors were efficiently rejected, whether or not CD4 T cells were present. This observation correlated with potent ex vivo cytotoxicity of brain-infiltrating CTLs, specific for the immunodominant epitope CW3_170–179 expressed on P815-CW3 tumor cells.

This article has been cited by other articles:

				M. Fujita, X. Zhu, K. Sasaki, R. Ueda, K. L. Low, I. F. Pollack, and H. Okada Inhibition of STAT3 Promotes the Efficacy of Adoptive Transfer Therapy Using Type-1 CTLs by Modulation of the Immunological Microenvironment in a Murine Intracranial Glioma J. Immunol., February 15, 2008; 180(4): 2089 - 2098. [Abstract] [Full Text] [PDF]

				F. Masson, T. Calzascia, W. Di Berardino-Besson, N. de Tribolet, P.-Y. Dietrich, and P. R. Walker Brain Microenvironment Promotes the Final Functional Maturation of Tumor-Specific Effector CD8+ T Cells J. Immunol., July 15, 2007; 179(2): 845 - 853. [Abstract] [Full Text] [PDF]

				J. Eguchi, M. Hatano, F. Nishimura, X. Zhu, J. E. Dusak, H. Sato, I. F. Pollack, W. J. Storkus, and H. Okada Identification of Interleukin-13 Receptor {alpha}2 Peptide Analogues Capable of Inducing Improved Antiglioma CTL Responses Cancer Res., June 1, 2006; 66(11): 5883 - 5891. [Abstract] [Full Text] [PDF]

				F. Nishimura, J. E. Dusak, J. Eguchi, X. Zhu, A. Gambotto, W. J. Storkus, and H. Okada Adoptive Transfer of Type 1 CTL Mediates Effective Anti-Central Nervous System Tumor Response: Critical Roles of IFN-Inducible Protein-10. Cancer Res., April 15, 2006; 66(8): 4478 - 4487. [Abstract] [Full Text] [PDF]

				N. Kuwashima, F. Nishimura, J. Eguchi, H. Sato, M. Hatano, T. Tsugawa, T. Sakaida, J. E. Dusak, W. K. Fellows-Mayle, G. D. Papworth, et al. Delivery of Dendritic Cells Engineered to Secrete IFN-{alpha} into Central Nervous System Tumors Enhances the Efficacy of Peripheral Tumor Cell Vaccines: Dependence on Apoptotic Pathways J. Immunol., August 15, 2005; 175(4): 2730 - 2740. [Abstract] [Full Text] [PDF]

				Y. Akasaki, G. Liu, N. H. C. Chung, M. Ehtesham, K. L. Black, and J. S. Yu Induction of a CD4+ T Regulatory Type 1 Response by Cyclooxygenase-2-Overexpressing Glioma J. Immunol., October 1, 2004; 173(7): 4352 - 4359. [Abstract] [Full Text] [PDF]

				T. Calzascia, W. Di Berardino-Besson, R. Wilmotte, F. Masson, N. d. Tribolet, P.-Y. Dietrich, and P. R. Walker Cutting Edge: Cross-Presentation as a Mechanism for Efficient Recruitment of Tumor-Specific CTL to the Brain J. Immunol., September 1, 2003; 171(5): 2187 - 2191. [Abstract] [Full Text] [PDF]