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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rodolfo, M. Articles by Colombo, M. P. Search for Related Content PubMed PubMed Citation Articles by Rodolfo, M. Articles by Colombo, M. P.

IL-4-Transduced Tumor Cell Vaccine Induces Immunoregulatory Type 2 CD8 T Lymphocytes That Cure Lung Metastases Upon Adoptive Transfer¹

Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy

Vaccinations with tumor cells engineered to produce IL-4 prolonged survival and cured 30% of mice bearing pulmonary metastases, an effect abrogated by in vivo depletion of T cells. Vaccination induced type 2 T cell polarization in both CD4 and CD8 T lymphocyte subsets. We focused on the antitumor activity exerted by type 2 CD8⁺ T cells (Tc2) activated by IL-4 tumor cell vaccination. Tc2 lymphocytes lacked in vitro tumor cytotoxicity, but released IL-4 upon stimulation with tumor cells, as shown by limiting dilution analysis of the frequencies of tumor-specific pCTL and of CD8 cells producing the cytokine. In vivo fresh purified CD8⁺ T lymphocytes from IL-4-vaccinated mice eliminated 80–100% of lung metastases when transferred into tumor-bearing mice. CD8⁺ lymphocytes from IL-4-vaccinated IFN- knockout (KO), but not from IL-4 KO, mice cured lung metastases, thus indicating that IL-4 produced by Tc2 cells was instrumental for tumor rejection. The antitumor effect of adoptively transferred Tc2 lymphocytes needed host CD8 T cells and AsGM1 leukocyte populations, and partially granulocytes. These data indicate that Tc2 CD8⁺ T cells exert immunoregulatory functions and induce tumor rejection through the cooperation of bystander lymphoid effector cells. Tumor eradication is thus not restricted to a type 1 response, but can also be mediated by a type 2 biased T cell response.

This article has been cited by other articles:

				Z. Li, F. Pradera, T. Kammertoens, B. Li, S. Liu, and Z. Qin Cross-Talk between T Cells and Innate Immune Cells Is Crucial for IFN-{gamma}-Dependent Tumor Rejection J. Immunol., August 1, 2007; 179(3): 1568 - 1576. [Abstract] [Full Text] [PDF]

				S. Olver, P. Groves, K. Buttigieg, E. S. Morris, M. L. Janas, A. Kelso, and N. Kienzle Tumor-Derived Interleukin-4 Reduces Tumor Clearance and Deviates the Cytokine and Granzyme Profile of Tumor-Induced CD8+ T Cells Cancer Res., January 1, 2006; 66(1): 571 - 580. [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]

				J. Eguchi, N. Kuwashima, M. Hatano, F. Nishimura, J. E. Dusak, W. J. Storkus, and H. Okada IL-4-Transfected Tumor Cell Vaccines Activate Tumor-Infiltrating Dendritic Cells and Promote Type-1 Immunity J. Immunol., June 1, 2005; 174(11): 7194 - 7201. [Abstract] [Full Text] [PDF]

				S. Gillessen, Y. N. Naumov, E. E. S. Nieuwenhuis, M. A. Exley, F. S. Lee, N. Mach, A. D. Luster, R. S. Blumberg, M. Taniguchi, S. P. Balk, et al. CD1d-restricted T cells regulate dendritic cell function and antitumor immunity in a granulocyte-macrophage colony-stimulating factor-dependent fashion PNAS, July 22, 2003; 100(15): 8874 - 8879. [Abstract] [Full Text] [PDF]

				K. M. M. Kelley, B. G. Rowan, and M. Ratnam Modulation of the Folate Receptor {alpha} Gene by the Estrogen Receptor: Mechanism and Implications in Tumor Targeting Cancer Res., June 1, 2003; 63(11): 2820 - 2828. [Abstract] [Full Text] [PDF]

				H. Hao, H. Qi, and M. Ratnam Modulation of the folate receptor type {beta} gene by coordinate actions of retinoic acid receptors at activator Sp1/ets and repressor AP-1 sites Blood, June 1, 2003; 101(11): 4551 - 4560. [Abstract] [Full Text] [PDF]

				S. Koido, Y. Tanaka, D. Chen, D. Kufe, and J. Gong The Kinetics of In Vivo Priming of CD4 and CD8 T Cells by Dendritic/Tumor Fusion Cells in MUC1-Transgenic Mice J. Immunol., March 1, 2002; 168(5): 2111 - 2117. [Abstract] [Full Text] [PDF]

				R. A. Kemp and F. Ronchese Tumor-Specific Tc1, But Not Tc2, Cells Deliver Protective Antitumor Immunity J. Immunol., December 1, 2001; 167(11): 6497 - 6502. [Abstract] [Full Text] [PDF]

				M. J. Dobrzanski, J. B. Reome, and R. W. Dutton Role of Effector Cell-Derived IL-4, IL-5, and Perforin in Early and Late Stages of Type 2 CD8 Effector Cell-Mediated Tumor Rejection J. Immunol., July 1, 2001; 167(1): 424 - 434. [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]