Immunocompromised tumor-bearing mice show a selective loss of STAT5a/b expression in T and B lymphocytes.
Impaired immune responses are frequently observed in tumor-bearing hosts during progression of tumor growth, but the molecular basis of these functional defects remains unclear. To investigate tumor-induced immunosuppression, we first established that lymphocytes from mice bearing s.c. mammary adenocarcinoma (TS/A) tumors were severely impaired in their ability to generate cellular and humoral Ag-specific responses. Lymphocytes from these mice were then screened for abnormalities in the expression of signal transducing proteins known to be involved in the regulation of cellular immunity. Interestingly, purified T and B cells isolated from immunocompromised tumor-bearing mice displayed a marked decrease in the transcription activators STAT5a and -b at the protein level and to a lesser extent at the mRNA level. By contrast, no change in the expression of STAT1, -3, and -6 or of the TCR itself were detected. The correlation in the loss of T and B cell function with the selective decrease in STAT5a/b expression suggests that regulation of the STAT5 signaling pathway may provide a molecular mechanism for modulating the immune system.
Pericle
F
F
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Kirken
R A
RA
Bronte
V
V
Sconocchia
G
G
DaSilva
L
L
Segal
D M
DM
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000276:immunology; D016867:Immunocompromised Host; D051379:Mice; D008807:Mice, Inbred BALB C; D008894:Milk Proteins; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D050799:STAT5 Transcription Factor; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000276:immunology
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; D015534:Trans-Activators