Immunomodulator OM 163-induced reversal of tumor-mediated immunosuppression and downregulation of TGF-β1 in vivo
article
Although PROb colonic tumor cells are immunosuppressive, the immunomodulator OM 163 induced the disappearance of macroscopic peritoneal nodules in 50% of rats bearing a peritoneal carcinomatosis (p.c.) induced by PROb cells. When the p.o. developed, the number of T lymphocytes was low and the expression of interferon (IFN)-γ mRNA in tumor nodules decreased very rapidly. The TGF-β1 secreted by PROb cells could be responsible for the immunosuppression, because the PROb cell supernatant inhibited IFN-γ production and T lymphocyte proliferation. When the rats were treated with OM 163, an infiltration of T lymphocytes was observed in tumor nodules, as well as a high expression of the IFN-γ mRNA. The antitumor efficiency of the immunomodulator OM 163 could be explained in part by a direct effect of OM 163 on T lymphocytes, because in vitro it stimulated the proliferation and the secretion of IFN-γ of T lymphocytes. OM 163 could also act at the TGF- β1 level. Although OM 163 alone or in combination with IFN-γ did not modify the TGF-β1 secretion by PROb cells in vitro, the expression of the TGF-β1 mRNA and the TGF-β1 protein content was decreased in vivo in treated tumor nodules.
Topics
Gamma interferonImmunomodulating agentInterleukin 2Messenger rnaTransforming growth factor beta1Unclassified drugAnimal cellAnimal experimentAnimal modelAnimal tissueAntineoplastic activityCarcinomatous peritonitisControlled studyFemaleImmune deficiencyImmunomodulationIntraperitoneal drug administrationLymphocyte proliferationMaleNonhumanRatT lymphocyteTumor cellAdjuvants, ImmunologicAnimalsAntineoplastic AgentsDose-Response Relationship, DrugDown-RegulationEscherichia coliGene ExpressionImmunosuppressionLymphocytesRNA, MessengerTransforming Growth Factor betaOM 163, 150104-43-1
TNO Identifier
233409
ISSN
0022-3565
Source
Journal of Pharmacology and Experimental Therapeutics, 278(2), pp. 926-933.
Pages
926-933
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