TY - JOUR
T1 - Impaired activation of tumoricidal function in macrophages from mammary tumor bearers
T2 - The role of IFN-γ
AU - Sotomayor, E. M.
AU - Cheng, X. F.
AU - Fu, Y. X.
AU - Hawkins, A.
AU - Calderon-Higginson, C.
AU - Lopez, D. M.
PY - 1993/1/1
Y1 - 1993/1/1
N2 - The growth of the D1-DMBA-3 mammary adenocarcinoma in BALB/c mice results in a profound deficit in the tumoricidal function of their peritoneal elicited macrophages (PEM) after stimulation with lipopolysaccharide (LPS). The capacity of these macrophages to respond to stronger signals, such as a combination of LPS and low levels (5 U/ml) of interferon-gamma (IFN-γ) is also impaired. Importantly, a combination of high levels (50 U/ml) of IFN-γ with 10 μg/ml of LPS, is able to trigger a cytolytic response in macrophages from tumor bearing mice against mammary tumor target cells, indicating that their lytic machinery is intact. However, IFN-γ production is severely diminished in T lymphocytes from tumor bearing mice as detected by ELISA, moreover, Northern blots revealed that the levels of IFN-γ RNA are also decreased in T cells from tumor bearers. The cooperation between T cells and macrophages is mediated, at least in part, by IFN-γ. Thus, mammary tumors have the potential to overcome host defenses, either by affecting the capacity of macrophages to respond adequately to activating agents, and/or by impairing the production of T-cell derived lymphokines important in macrophage activation for tumor killing.
AB - The growth of the D1-DMBA-3 mammary adenocarcinoma in BALB/c mice results in a profound deficit in the tumoricidal function of their peritoneal elicited macrophages (PEM) after stimulation with lipopolysaccharide (LPS). The capacity of these macrophages to respond to stronger signals, such as a combination of LPS and low levels (5 U/ml) of interferon-gamma (IFN-γ) is also impaired. Importantly, a combination of high levels (50 U/ml) of IFN-γ with 10 μg/ml of LPS, is able to trigger a cytolytic response in macrophages from tumor bearing mice against mammary tumor target cells, indicating that their lytic machinery is intact. However, IFN-γ production is severely diminished in T lymphocytes from tumor bearing mice as detected by ELISA, moreover, Northern blots revealed that the levels of IFN-γ RNA are also decreased in T cells from tumor bearers. The cooperation between T cells and macrophages is mediated, at least in part, by IFN-γ. Thus, mammary tumors have the potential to overcome host defenses, either by affecting the capacity of macrophages to respond adequately to activating agents, and/or by impairing the production of T-cell derived lymphokines important in macrophage activation for tumor killing.
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M3 - Article
AN - SCOPUS:0027368542
VL - 3
SP - 719
EP - 727
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 4
ER -