| 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 p56(lck) and p59(fyn), as well as the TCR-ΞΆ-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. |
| Keywords: |
signal transduction; controlled study; protein phosphorylation; proto-oncogene proteins; nonhuman; flow cytometry; cd3 antigen; t lymphocyte; t-lymphocytes; animal cell; mouse; animal; mice; interleukin 2; spleen; tumor volume; animal model; membrane proteins; calcium; protein tyrosine kinase; tyrosine; mice, inbred balb c; t lymphocyte receptor; fibrosarcoma; receptors, antigen, t-cell; immunoblotting; tumor growth; complementary dna; retrovirus; interleukin-2; polyacrylamide gel electrophoresis; virus vector; calcium transport; lymphocyte specific protein tyrosine kinase p56(lck); protein-tyrosine kinase; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; receptor-cd3 complex, antigen, t-cell
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