Modulation of human tumor associated macrophages from malignant effusions with cytokines and proteolytic enzymes
Mohr T. (1); Závadová E. (1); Hauptmann E. (1); Maca S. (2); Neumann M. (3); Salzer H. (4); Micksche M. (1)
1 Institute for Tumorbiology - Cancer Research, Dept.
For Applied & Experimental Oncology, Vienna, Austria
2 Hospital Lainz, 5th Medical Department
3 First Internal Department, Centre for Pulmonary Disease, Vienna, Austria
4 Department for Gynaecology, Wilhelminenspital, Vienna, Austria
The European Journal of Cancer 1999; 35(4): No. 1448, 357.
Tumor associated macrophages (TAMs) represent a major component of
the lymphoreticular infiltrate of human tumors, malignant pleural effusions
and malignant ascites. TAMs are functionally involved in anti-tumor
defense via cytotoxic activities such as f.i. direct cellular cytotoxicity
and release of cytokines. They also have the capacity to affect aspects
of the biology of neoplastic tissues like vascularization, growth rate,
stroma formation and dissolution. The objective of this study was to
investigate the effect of various cytokines (GM-CSF, IFN-g,
IL-1b and IFN-a)
and polyenzyme preparation, on the functional activity of TAMs isolated
from malignant effusions of patients with ovarian, breast and lung cancer.
TAMs were isolated by density centrifugation over a discontinuous Ficoll-Hypaque
gradient. Peripheral blood monocyte derived macrophages (PBMMs) - serving
as controls - were obtained using a combination of density centrifugation
and selective adhesion followed by incubation with GM-CSF. The expression
of cytokines was determined on mRNA-level via RT-PCR and on protein
level via ELISAs. Biologically active TNF-a
as well as cellular cytotoxicity were determined using bio-assays.
The activation status of TAMs differed markedly from that of PBMMs.
TAMs showed a significantly lower IL-1b production
and higher TGF-b production. Cellular cytotoxicity was markedly lower in
TAMs when compared to PBM derived macrophages. The tested cytokines,
especially GM-CSF as well as the polyenzyme preparation were able to
induce and increase the production of TNF-a and to enhance the cellular cytotoxicity. A decreased TGF-b production on mRNA and protein level was observed in TAMs
treated with cytokines or the polyenzyme preparation.
TAMs are one of the immune system's representatives at the host-tumor
interface and reflect in some way the failure of the host to have immunologically
controlled the tumor. TAMs represent a promising target to therapeutic
intervention. With this study we demonstrated that it is possible to
stimulate in vitro the functional activity of TAMs by treatment
with cytokines or polyenzyme preparations. This might elucidate of the
role of macrophages and especially TAMs in tumor defense.
Lék pro vnitřní užití. Čtěte pečlivě příbalovou
informaci.
Inzertní stránky společnosti MUCOS Pharma CZ, s.r.o. - tel: (+420)-267 750
003