Tumor-Derived Interleukin-4 Reduces Tumor Clearance and Deviates the Cytokine and Granzyme Profile of Tumor-Induced CD8+ T Cells
| Autor: | Anne Kelso, Michelle L. Janas, Norbert Kienzle, Stuart D. Olver, Kathy Buttigieg, Edward S. Morris, Penny Groves |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Antigen presentation Gene Expression HLA-C Antigens CD8-Positive T-Lymphocytes Transfection Mice Immune system Cell Line Tumor medicine Animals Cytotoxic T cell Interleukin 4 biology Mastocytoma Tumor-Derived medicine.disease Primary tumor Oncology Granzyme Mice Inbred DBA Immunology biology.protein Cancer research Female Interleukin-4 T-Lymphocytes Cytotoxic |
| Zdroj: | Cancer Research. 66:571-580 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | An interleukin (IL)-4-containing tumor environment is reported to be beneficial for immune clearance of tumor cells in vivo; however, the effect of IL-4 on the effector CD8+ T cells contributing to tumor clearance is not well defined. We have used the immunogenic HLA-CW3-expressing P815 (P.CW3) mastocytoma and investigated whether IL-4 expression by the tumor affects tumor clearance and, if so, whether it alters the tumor-induced Vβ10+ CD8+ T-cell response. P.CW3 were stably transfected with IL-4 or the empty control vector, and independent cell lines were injected i.p. into syngeneic DBA/2 mice. After apparent clearance of primary tumors over 12 to 15 days, secondary tumors arose that lacked surface expression and H-2-restricted antigen presentation of CW3 in part due to the loss of the HLA-CW3 expression cassette. Surprisingly, mice that received IL-4-producing tumor cells showed delayed primary tumor clearance and were significantly more prone to develop secondary tumors compared with mice receiving control tumor cells. Tumor clearance was dependent on CD8+ T cells. The IL-4-secreting P.CW3 tumor cells led to markedly higher mRNA expression of IL-4 and granzyme A and B but no differences in IFN-γ and IL-2 production, cell proliferation, or ex vivo CTL activity in primary Vβ10+ CD8+ T cells when compared with the control tumor cells. We concluded that tumor-derived IL-4 selectively changed the quality of the tumor-induced CD8+ T-cell response and resulted in unexpected negative effects on tumor clearance. These data bring into question the delivery of IL-4 to the tumor environment for improving tumor immunotherapy. (Cancer Res 2006; 66(1): 571-80) |
| Databáze: | OpenAIRE |
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