| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,,§
*
Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR 97213;
Department of Biochemistry and Molecular Biology, Oregon Graduate Institute, Portland, OR 97291; and
Oregon Cancer Center and
§
Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR 97201
The requirement for CD4+ Th cells in the cross-priming of antitumor CTL is well accepted in tumor immunology. Here we report that the requirement for T cell help can be replaced by local production of GM-CSF at the vaccine site. Experiments using mice in which CD4+ T cells were eliminated, either by Ab depletion or by gene knockout of the MHC class II ß-chain (MHC II KO), revealed that priming of therapeutic CD8+ effector T cells following vaccination with a GM-CSF-transduced B16BL6-D5 tumor cell line occurred independently of CD4+ T cell help. The adoptive transfer of CD8+ effector T cells, but not CD4+ effector T cells, led to complete regression of pulmonary metastases. Regression of pulmonary metastases did not require either host T cells or NK cells. Transfer of CD8+ effector T cells alone could cure wild-type animals of systemic tumor; the majority of tumor-bearing mice survived long term after treatment (>100 days). In contrast, adoptive transfer of CD8+ T cells to tumor-bearing MHC II KO mice improved survival, but eventually all MHC II KO mice succumbed to metastatic disease. WT mice cured by adoptive transfer of CD8+ T cells were resistant to tumor challenge. Resistance was mediated by CD8+ T cells in mice at 50 days, while both CD4+ and CD8+ T cells were important for protection in mice challenged 150 days following adoptive transfer. Thus, in this tumor model CD4+ Th cells are not required for the priming phase of CD8+ effector T cells; however, they are critical for both the complete elimination of tumor and the maintenance of a long term protective antitumor memory response in vivo.
This article has been cited by other articles:
|
|
 |
|
  W. S. Webster, R. H. Thompson, K. J. Harris, X. Frigola, S. Kuntz, B. A. Inman, and H. Dong Targeting Molecular and Cellular Inhibitory Mechanisms for Improvement of Antitumor Memory Responses Reactivated by Tumor Cell Vaccine J. Immunol., September 1, 2007; 179(5): 2860 - 2869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. S. Zimmermann, A. Casati, C. Schiering, S. Caserta, R. Hess Michelini, V. Basso, and A. Mondino Tumors Hamper the Immunogenic Competence of CD4+ T Cell-Directed Dendritic Cell Vaccination J. Immunol., September 1, 2007; 179(5): 2899 - 2909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Sussman, R. Parihar, K. Winstead, and F. D. Finkelman Prolonged Culture of Vaccine-Primed Lymphocytes Results in Decreased Antitumor Killing and Change in Cytokine Secretion Cancer Res., December 15, 2004; 64(24): 9124 - 9130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, M. Santosuosso, P. Ngai, A. Zganiacz, and Z. Xing Activation of CD8 T Cells by Mycobacterial Vaccination Protects against Pulmonary Tuberculosis in the Absence of CD4 T Cells J. Immunol., October 1, 2004; 173(7): 4590 - 4597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Maraskovsky, S. Sjolander, D. P. Drane, M. Schnurr, T. T. T. Le, L. Mateo, T. Luft, K.-A. Masterman, T.-Y. Tai, Q. Chen, et al. NY-ESO-1 Protein Formulated in ISCOMATRIX Adjuvant Is a Potent Anticancer Vaccine Inducing Both Humoral and CD8+ T-Cell-Mediated Immunity and Protection against NY-ESO-1+ Tumors Clin. Cancer Res., April 15, 2004; 10(8): 2879 - 2890. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
Y. Lu, Y.-q. Wei, L. Tian, X. Zhao, L. Yang, B. Hu, B. Kan, Y.-j. Wen, F. Liu, H.-x. Deng, et al. Immunogene Therapy of Tumors with Vaccine Based on Xenogeneic Epidermal Growth Factor Receptor J. Immunol., March 15, 2003; 170(6): 3162 - 3170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Poehlein, H.-M. Hu, J. Yamada, I. Assmann, W. G. Alvord, W. J. Urba, and B. A. Fox TNF Plays an Essential Role in Tumor Regression after Adoptive Transfer of Perforin/IFN-{gamma} Double Knockout Effector T Cells J. Immunol., February 15, 2003; 170(4): 2004 - 2013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. G. Gao, V. Khammanivong, W. J. Liu, G. R. Leggatt, I. H. Frazer, and G. J. P. Fernando Antigen-specific CD4+ T-Cell Help Is Required to Activate a Memory CD8+ T Cell to a Fully Functional Tumor Killer Cell Cancer Res., November 15, 2002; 62(22): 6438 - 6441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-M. Hu, H. Winter, J. Ma, M. Croft, W. J. Urba, and B. A. Fox CD28, TNF Receptor, and IL-12 Are Critical for CD4-Independent Cross-Priming of Therapeutic Antitumor CD8+ T Cells J. Immunol., November 1, 2002; 169(9): 4897 - 4904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-M. Hu, C. H. Poehlein, W. J. Urba, and B. A. Fox Development of Antitumor Immune Responses in Reconstituted Lymphopenic Hosts Cancer Res., July 15, 2002; 62(14): 3914 - 3919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ribas, L. H. Butterfield, S. N. Amarnani, V. B. Dissette, D. Kim, W. S. Meng, G. A. Miranda, H.-J. Wang, W. H. McBride, J. A. Glaspy, et al. CD40 Cross-Linking Bypasses the Absolute Requirement for CD4 T Cells during Immunization with Melanoma Antigen Gene-modified Dendritic Cells Cancer Res., December 1, 2001; 61(24): 8787 - 8793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Velders, S. McElhiney, M. C. Cassetti, G. L. Eiben, T. Higgins, G. R. Kovacs, A. G. Elmishad, W. M. Kast, and L. R. Smith Eradication of Established Tumors by Vaccination with Venezuelan Equine Encephalitis Virus Replicon Particles Delivering Human Papillomavirus 16 E7 RNA Cancer Res., November 1, 2001; 61(21): 7861 - 7867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Winter, H.-M. Hu, K. McClain, W. J. Urba, and B. A. Fox Immunotherapy of Melanoma: A Dichotomy in the Requirement for IFN-{{gamma}} in Vaccine-Induced Antitumor Immunity Versus Adoptive Immunotherapy J. Immunol., June 15, 2001; 166(12): 7370 - 7380. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
