This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Olver, S. Articles by Kienzle, N. Search for Related Content PubMed PubMed Citation Articles by Olver, S. Articles by Kienzle, N.

Tumor-Derived Interleukin-4 Reduces Tumor Clearance and Deviates the Cytokine and Granzyme Profile of Tumor-Induced CD8⁺ T Cells

¹ Cooperative Research Centre for Vaccine Technology and ² Queensland Institute of Medical Research, Brisbane, Queensland, Australia

Requests for reprints: Norbert Kienzle, Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia. Phone: 61-7-3362-0379; Fax: 61-7-3362-0105; E-mail: norbert.kienzle{at}qimr.edu.au.

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 Vß10⁺ 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- and IL-2 production, cell proliferation, or ex vivo CTL activity in primary Vß10⁺ 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)

This article has been cited by other articles:

				S. H. Apte, A. Baz, P. Groves, A. Kelso, and N. Kienzle Interferon-{gamma} and interleukin-4 reciprocally regulate CD8 expression in CD8+ T cells PNAS, November 11, 2008; 105(45): 17475 - 17480. [Abstract] [Full Text] [PDF]