RT Journal Article
SR Electronic
T1 Prevention and reversal of tumor cell-induced monocyte deactivation by cytokines, purified protein derivative (PPD), and anti-IL-10 antibody
JF Cancer Immunity Archive
JO Cancer Immun
FD American Association for Cancer Research
SP 8
VO 4
IS 1
A1 Baj-Krzyworzeka, Monika
A1 Baran, Jaroslaw
A1 Szatanek, Rafal
A1 Stankiewicz, Danuta
A1 Siedlar, Maciej
A1 Zembala, Marek
YR 2004
UL http://cancerimmunolres.aacrjournals.org/content/4/1/8.abstract
AB Upon contact with tumor cells when cocultured in vitro, human monocytes become unresponsive (deactivated) to restimulation and demonstrate decreased production of TNF-alpha and IL-12, and enhanced IL-10 secretion. The present study was undertaken to determine whether immunomodulatory agents (proinflammatory cytokines and PPD of tuberculin) could either prevent or reverse the deactivation of monocytes. Monocytes were treated with the agents either before or after being cocultured with tumor cells. Pretreatment of monocytes with IFN-gamma, either alone or in combination with TNF-alpha, GM-CSF, or PPD, significantly enhanced TNF-alpha and IL-12 production by deactivated monocytes. TNF-alpha, GM-CSF, and PPD alone were inactive. Treatment of monocytes following coculture with IFN-gamma, TNF-alpha, GM-CSF, PPD or IFN-gamma in combination with these agents reversed the depressed TNF-alpha release, whereas IL-12 production was enhanced by IFN-gamma alone. All the agents had no or only a limited effect on the enhanced IL-10 secretion by deactivated monocytes. However, treatment of cocultured monocytes with anti-IL-10 mAb significantly increased the production of TNF-alpha and IL-12 by deactivated monocytes. Moreover, coengraftment of deactivated monocytes with human pancreatic carcinoma cells into SCID mice caused an enhancement of the tumor growth that was alleviated by the treatment of monocytes in vitro with IFN-gamma alone or in combination with GM-CSF or PPD. These results suggest that activation of monocytes with certain proinflammatory cytokines and/or selective inhibition of IL-10 by a mAb may prevent or reverse monocyte deactivation caused by tumor cells. This article was published in Cancer Immunity, a Cancer Research Institute journal that ceased publication in 2013 and is now provided online in association with Cancer Immunology Research.