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The Observation of Immunosuppressor(s) Derived from Cultured Thmor Cells and Its Partial Neutralization with OK-432

ADISAK WONGKAJORNSILP, M.D., Ph.D.*, RUNG-ARUNE LUANKOSOLCHAI, M.S.*, SU:KIT HUABPRASERT*, VORAVUT CliANYAVANICH,M.D.**, NANTASAK TISAVIPAT, M.D.**, PRASIT W ATANAPA, M.D., Ph.D.**

Affiliation : * Department of Pharmacology, **Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

Abstract
Malignant tumors such as brain tumors have been reported to be associated with immunosuppression caused by certain tumor-secreted cytokines. The reversion of tumor-derived immunosuppression has not been described. The use of OK-432, an immunomodulat>ry agent prepared from Su-strain of Streptococcus pyogenes A3, to activate peripheral blood mononuclear cells from a patient with glioblastoma multiforme has demonstrated a sharp rise in proliferative response. This proliferative response was compromised in the presence of living and irradiated autogeneic cancer cells. The conditioned media from cultured cells of glioblastoma multiforme, astrocytoma, and cholangiocarcinoma were tested for immuno suppressive ability. We found that conditioned media from 3 of 4 cases of glioblastoma, all 3 cases of astrocytoma, and 1 case of cholangiocarcinoma exhibited immunosuppressive activity toward the proliferative response of allogeneic peripheral blood mononuclear cells to phytohemagglutinin. This is the first report that cholangiocarcinoma produces soluble immunosuppressor(s). Our finding suggested that soluble substance(s) as well as direct cell-cell contact between tumor cells and mononuclear cells play roles in the observed tumor derived immunosuppression.

Keywords : Cancer, lmmunosuppressor, Immunomodulator, Cholangiocarcinoma, Brain Tumor, Glioblastoma Multiforme, Astrocytoma


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