| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048
For unknown reasons, advanced age remains a dominant predictor of poor clinical outcome for nearly all cancers. A decrease in the production of T cells by the thymus accompanies normal aging and parallels the age-dependent increase in cancer progression, but the specific impact of immunity on tumor progression in general is unknown. Glioblastoma multiforme (GBM), the most common primary brain neoplasm, is characterized by rapid age-dependent rates of progression and death. In this study, we show levels of CD8+ recent thymic emigrants (RTEs) accounted for the prognostic power of age on clinical outcome in GBM patients. CD8+ RTEs, typically a tiny proportion of CD8+ T cells, remarkably accounted for the majority of tumor Ag-binding small precursor cells in PBMC from these patients and from healthy individuals. Large blasting tumor Ag-binding cells comprised of CD8+ RTEs and phenotypically related cells were predominantly expanded following experimental vaccination of GBM patients. Quantification of CD8+ RTE expansion in vivo correlated strongly with vaccine-elicited cytokine responses, and estimated numbers of expanding CD8+ RTEs were consistent predictors of clinical outcome in vaccinated GBM patients. Targeted mutant (CD8
-/-) mice specifically deficient in thymic CD8+ T cell production uniquely displayed an age-specific decrease in glioma host survival as well as a strong correlation between host survival and thymus cellular production. These findings suggest that levels and function of newly produced CD8+ T cells critically influence age-dependent cancer mortality and exert one of the strongest known influences on GBM outcome by predominantly mediating clinically beneficial antitumor immune responses.
This article has been cited by other articles:
|
|
 |
|
  C. J. Wheeler, K. L. Black, G. Liu, M. Mazer, X.-x. Zhang, S. Pepkowitz, D. Goldfinger, H. Ng, D. Irvin, and J. S. Yu Vaccination Elicits Correlated Immune and Clinical Responses in Glioblastoma Multiforme Patients Cancer Res., July 15, 2008; 68(14): 5955 - 5964. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Galarneau, J. Villeneuve, G. Gowing, J.-P. Julien, and L. Vallieres Increased Glioma Growth in Mice Depleted of Macrophages Cancer Res., September 15, 2007; 67(18): 8874 - 8881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Fecci, D. A. Mitchell, J. F. Whitesides, W. Xie, A. H. Friedman, G. E. Archer, J. E. Herndon II, D. D. Bigner, G. Dranoff, and J. H. Sampson Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res., March 15, 2006; 66(6): 3294 - 3302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Glass, M. Synowitz, G. Kronenberg, J.-H. Walzlein, D. S. Markovic, L.-P. Wang, D. Gast, J. Kiwit, G. Kempermann, and H. Kettenmann Glioblastoma-Induced Attraction of Endogenous Neural Precursor Cells Is Associated with Improved Survival J. Neurosci., March 9, 2005; 25(10): 2637 - 2646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Wheeler, A. Das, G. Liu, J. S. Yu, and K. L. Black Clinical Responsiveness of Glioblastoma Multiforme to Chemotherapy after Vaccination Clin. Cancer Res., August 15, 2004; 10(16): 5316 - 5326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Yu, G. Liu, H. Ying, W. H. Yong, K. L. Black, and C. J. Wheeler Vaccination with Tumor Lysate-Pulsed Dendritic Cells Elicits Antigen-Specific, Cytotoxic T-Cells in Patients with Malignant Glioma Cancer Res., July 15, 2004; 64(14): 4973 - 4979. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
