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Abnormal signal transduction by T cells of mice with parental tumors is not seen in mice bearing IL-2-secreting tumors.

S Salvadori, B Gansbacher, A M Pizzimenti and K S Zier
J Immunol December 1, 1994, 153 (11) 5176-5182;
S Salvadori
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B Gansbacher
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A M Pizzimenti
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K S Zier
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Abstract

There is considerable evidence to demonstrate that immune function is abnormal in tumor-bearing mice, perhaps accounting, at least in part, for progressive tumor growth. In an attempt to generate an antitumor response, we used retroviral vectors to express IL-2 cDNA in CMS5, a murine fibrosarcoma. Mice inoculated with unmodified tumor cells suffered progressive tumor growth, whereas tumors secreting IL-2 were rejected or grew slowly. Animals bearing unmodified but not IL-2-secreting tumors also were immunosuppressed. On the basis of these observations, we were interested in how IL-2 secretion by the tumor cells prevented the onset of hyporesponsiveness. To identify biochemical differences between T cells of mice with parental vs slowly growing IL-2-secreting tumors, we examined signal transduction after activation through the CD3/TCR complex. Protein tyrosine phosphorylation was altered and calcium flux was reduced in cells of mice with parental tumors compared with animals with slowly growing IL-2-secreting tumors. In addition, levels of protein for the tyrosine kinases p56lck and p59fyn, as well as the TCR-zeta-chain, were reduced. These differences in signal transduction were observed for T cells of mice with parental and IL-2-secreting tumors of the same size, demonstrating that differences in tumor size alone could not explain our findings. Thus, IL-2 secretion by tumors seems to be able to prevent immunosuppression by maintaining normal signal transduction in T cells, facilitating the generation of antitumor responses.

  • Copyright © 1994 by American Association of Immunologists

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The Journal of Immunology
Vol. 153, Issue 11
1 Dec 1994
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Abnormal signal transduction by T cells of mice with parental tumors is not seen in mice bearing IL-2-secreting tumors.
S Salvadori, B Gansbacher, A M Pizzimenti, K S Zier
The Journal of Immunology December 1, 1994, 153 (11) 5176-5182;

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Abnormal signal transduction by T cells of mice with parental tumors is not seen in mice bearing IL-2-secreting tumors.
S Salvadori, B Gansbacher, A M Pizzimenti, K S Zier
The Journal of Immunology December 1, 1994, 153 (11) 5176-5182;
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Print ISSN 0022-1767        Online ISSN 1550-6606