Immunotherapy of Cytotoxic T Cell-resistant Tumors by T Helper 2 Cells: An Exotaxin and STAT6-dependent Process
Date
2003
Authors
Mattes, Joerg
Hulett, Mark
Xie, Wei
Hogan, Simon
Rothenberg, Marc E
Foster, Paul S
Parish, Christopher
Journal Title
Journal ISSN
Volume Title
Publisher
Rockefeller University Press
Abstract
Currently most attempts at cancer immunotherapy involve the generation of CD8+ cytotoxic T lymphocytes (CTLs) against tumor-associated antigens. Many tumors, however, have been immunoselected to evade recognition by CTLs and thus alternative approaches to cancer immunotherapy are urgently needed. Here we demonstrate that CD4+ T cells that recognize a secreted tumor-specific antigen and exhibit a cytokine secretion profile characteristic of Th2 cells, are capable of clearing established lung and visceral metastases of a CTL-resistant melanoma. Clearance of lung metastases by the Th2 cells was found to be totally dependent on the eosinophil chemokine, eotaxin, and partially dependent on the transcription activator signal transducer and activator of transcription 6 (STAT6), with degranulating eosinophils within the tumors inducing tumor regression. In contrast, tumor-specific CD4+ Th1 cells, that recruited macrophages into the tumors, had no effect on tumor growth. This work provides the basis for a new approach to adoptive T cell immunotherapy of cancer.
Description
Keywords
Keywords: CD4 antigen; CD8 antigen; cytokine; eotaxin; gamma interferon; interleukin 4; monoclonal antibody; ovalbumin; STAT6 protein; animal cell; animal model; article; cancer immunotherapy; controlled study; cytotoxic T lymphocyte; cytotoxicity; helper cell; mel Eosinophils; Eotaxin; Immune evasion; Th2 cells; Tumor immunotherapy
Citation
Collections
Source
Journal of Experimental Medicine
Type
Journal article