IL-21 activates both innate and adaptive immunity to generate potent antitumor responses that require perforin but are independent of IFN-gamma
| Autor: | Michael J. Grusby, Deborah A. Young, Mayra Senices, Matthew J. Whitters, Kyriaki Dunussi-Joannopoulos, Hak-Ling Ma, T. Mary Collins, Richard F. Konz |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Cytotoxicity
Immunologic Pore Forming Cytotoxic Proteins medicine.medical_treatment T cell Immunology Melanoma Experimental Mice Nude Mice SCID Cancer Vaccines Interferon-gamma Mice Immune system Adjuvants Immunologic In vivo Antigens Neoplasm Transduction Genetic medicine Tumor Cells Cultured Immunology and Allergy Animals Fibrosarcoma Mice Knockout Mice Inbred BALB C Membrane Glycoproteins biology Perforin Interleukins Interleukin-21 Receptor alpha Subunit Immunotherapy Receptors Interleukin Acquired immune system medicine.disease Interleukin-12 Growth Inhibitors Immunity Innate Interleukin-10 Mice Inbred C57BL medicine.anatomical_structure Immunity Active biology.protein Female Receptors Interleukin-21 Interleukin-4 Sarcoma Experimental CD8 Cell Division T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 171(2) |
| ISSN: | 0022-1767 |
| Popis: | IL-21 is a key factor in the transition between innate and adaptive immune responses. We have used the cytokine gene therapy approach to study the antitumor responses mediated by IL-21 in the B16F1 melanoma and MethA fibrosarcoma tumor models in mice. Retrovirally transduced tumor cells secreting biologically functional IL-21 have growth patterns in vitro similar to that of control green fluorescent protein-transduced cells, but are completely rejected in vivo. We show that IL-21 activates NK and CD8+ T cells in vivo, thus mediating complete rejection of poorly immunogenic tumors. Rejection of IL-21-secreting tumors requires the presence of cognate IL-21R and does not depend on CD4+ T cell help. Interestingly, perforin, but not IFN-γ or other major Th1 and Th2 cytokines (IL-12, IL-4, or IL-10), is required for the IL-21-mediated antitumor response. Moreover, IL-21 results in 50% protection and 70% cure of nonimmunogenic tumors when given before and after tumor challenge, respectively, in C57BL/6 mice. We conclude that IL-21 immunotherapy warrants clinical evaluation as a potential treatment for cancer. |
| Databáze: | OpenAIRE |
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