| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, and
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
The functional status of circulating vaccine-induced, tumor-specific T cells has been questioned to explain their paradoxical inability to inhibit tumor growth. We enumerated with HLA-A*0201/peptide tetramers (tHLA) vaccine-elicited CD8+ T cell precursor frequency among PBMC in 13 patients with melanoma undergoing vaccination with the HLA-A*0201-associated gp100:209–217(210 M) epitope. T cell precursor frequency increased from undetectable to 12,400 ± 3,600 x 106 CD8+ T cells after vaccination and appeared heterogeneous according to previously described functional subtypes: CD45RA+CD27+ (14 ± 2.6% of tHLA-staining T cells), naive; CD45RA-CD27+ (14 ± 3.2%), memory; CD45RA+CD27- (43 ± 6%), effector; and CD45RA-CD27- (30 ± 4.1%), memory/effector. The majority of tHLA+CD8+ T cells displayed an effector, CD27- phenotype (73%). However, few expressed perforin (17%). Epitope-specific in vitro stimulation (IVS) followed by 10-day expansion in IL-2 reversed this phenotype by increasing the number of perforin+ (84 ± 3.6%; by paired t test, p < 0.001) and CD27+ (from 28 to 67%; by paired t test, p = 0.01) tHLA+ T cells. This conversion probably represented a change in the functional status of tHLA+ T cells rather than a preferential expansion of a CD27+ (naive and/or memory) PBMC, because it was reproduced after IVS of a T cell clone bearing a classic effector phenotype (CD45RA+CD27-). These findings suggest that circulating vaccine-elicited T cells are not as functionally active as inferred by characterization of IVS-induced CTL. In addition, CD45RA/CD27 expression may be more informative about the status of activation of circulating T cells than their status of differentiation.
This article has been cited by other articles:
|
|
 |
|
  A. Scardino, M. Alimandi, P. Correale, S. G. Smith, R. Bei, H. Firat, M. G. Cusi, O. Faure, S. Graf-Dubois, G. Cencioni, et al. A Polyepitope DNA Vaccine Targeted to Her-2/ErbB-2 Elicits a Broad Range of Human and Murine CTL Effectors to Protect against Tumor Challenge Cancer Res., July 15, 2007; 67(14): 7028 - 7036. [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]
|
|
|
|
 |
|
 H. S. Bashyam, S. Green, and A. L. Rothman Dengue Virus-Reactive CD8+ T Cells Display Quantitative and Qualitative Differences in Their Response to Variant Epitopes of Heterologous Viral Serotypes. J. Immunol., March 1, 2006; 176(5): 2817 - 2824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yang, K.-Y. Tsang, and J. Schlom Induction of Higher-Avidity Human CTLs by Vector-Mediated Enhanced Costimulation of Antigen-Presenting Cells Clin. Cancer Res., August 1, 2005; 11(15): 5603 - 5615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Chen, J. Hou, X. Jiang, S. Ma, M. Meng, B. Wang, M. Zhang, M. Zhang, X. Tang, F. Zhang, et al. Response of Memory CD8+ T Cells to Severe Acute Respiratory Syndrome (SARS) Coronavirus in Recovered SARS Patients and Healthy Individuals J. Immunol., July 1, 2005; 175(1): 591 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Monsurro, E. Wang, Y. Yamano, S. A. Migueles, M. C. Panelli, K. Smith, D. Nagorsen, M. Connors, S. Jacobson, and F. M. Marincola Quiescent phenotype of tumor-specific CD8+ T cells following immunization Blood, October 1, 2004; 104(7): 1970 - 1978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Oka, A. Tsuboi, T. Taguchi, T. Osaki, T. Kyo, H. Nakajima, O. A. Elisseeva, Y. Oji, M. Kawakami, K. Ikegame, et al. Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression PNAS, September 21, 2004; 101(38): 13885 - 13890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Hanson, S. S. Kang, L. A. Norian, K. Matsui, L. A. O'Mara, and P. M. Allen CD4-Directed Peptide Vaccination Augments an Antitumor Response, but Efficacy Is Limited by the Number of CD8+ T Cell Precursors J. Immunol., April 1, 2004; 172(7): 4215 - 4224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Dobrzanski, J. B. Reome, J. A. Hollenbaugh, and R. W. Dutton Tc1 and Tc2 Effector Cell Therapy Elicit Long-Term Tumor Immunity by Contrasting Mechanisms That Result in Complementary Endogenous Type 1 Antitumor Responses J. Immunol., February 1, 2004; 172(3): 1380 - 1390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Walker, D. Haley, W. Miller, K. Floyd, K. P. Wisner, N. Sanjuan, H. Maecker, P. Romero, H.-M. Hu, W. G. Alvord, et al. gp100209-2M Peptide Immunization of Human Lymphocyte Antigen-A2+ Stage I-III Melanoma Patients Induces Significant Increase in Antigen-Specific Effector and Long-Term Memory CD8+ T Cells Clin. Cancer Res., January 15, 2004; 10(2): 668 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Dobrzanski, J. B. Reome, J. A. Hollenbaugh, J. C. Hylind, and R. W. Dutton Effector Cell-Derived Lymphotoxin {alpha} and Fas Ligand, but not Perforin, Promote Tc1 and Tc2 Effector Cell-Mediated Tumor Therapy in Established Pulmonary Metastases Cancer Res., January 1, 2004; 64(1): 406 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Nagorsen, C. Scheibenbogen, F. M. Marincola, A. Letsch, and U. Keilholz Natural T Cell Immunity against Cancer Clin. Cancer Res., October 1, 2003; 9(12): 4296 - 4303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Anichini, A. Scarito, A. Molla, G. Parmiani, and R. Mortarini Differentiation of CD8+ T Cells from Tumor-Invaded and Tumor-Free Lymph Nodes of Melanoma Patients: Role of Common {gamma}-Chain Cytokines J. Immunol., August 15, 2003; 171(4): 2134 - 2141. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
