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Tumor-derived interleukin-4 reduces tumor clearance and deviates the cytokine and granzyme profile of tumor-induced CD8+ T cells.
- Source :
-
Cancer research [Cancer Res] 2006 Jan 01; Vol. 66 (1), pp. 571-80. - Publication Year :
- 2006
-
Abstract
- 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 Vbeta10+ 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-gamma and IL-2 production, cell proliferation, or ex vivo CTL activity in primary Vbeta10+ 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.
- Subjects :
- Animals
Cell Line, Tumor
Female
Gene Expression
HLA-C Antigens immunology
Interleukin-4 biosynthesis
Interleukin-4 genetics
Mastocytoma genetics
Mice
Mice, Inbred DBA
T-Lymphocytes, Cytotoxic immunology
Transfection
CD8-Positive T-Lymphocytes immunology
Interleukin-4 immunology
Mastocytoma immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 66
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 16397274
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-05-1362