Essential Requirement of Toll-like Receptor 4 Expression on CD11c+ Cells for Locoregional Immunotherapy of Malignant Ascites Using a Streptococcal Preparation OK-432

Toll-like receptors (TLRs) are important molecules that stimulate the innate immunity in order to eradicate microbial pathogens, after which the adaptive immunity emerges. The involvement of TLRs in the action mechanism of OK-432, a bacterial preparation, was investigated in the locoregional treatme...

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Veröffentlicht in:Anticancer research 2006-09, Vol.26 (5B), p.3701-3707
Hauptverfasser: HIRONAKA, Katsuji, YAMAGUCHI, Yoshiyuki, OKITA, Riki, OKAWAKI, Makoto, NAGAMINE, Ichiro
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container_title Anticancer research
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creator HIRONAKA, Katsuji
YAMAGUCHI, Yoshiyuki
OKITA, Riki
OKAWAKI, Makoto
NAGAMINE, Ichiro
description Toll-like receptors (TLRs) are important molecules that stimulate the innate immunity in order to eradicate microbial pathogens, after which the adaptive immunity emerges. The involvement of TLRs in the action mechanism of OK-432, a bacterial preparation, was investigated in the locoregional treatment of malignant ascites from gastric cancer. The expression of TLRs in ascites cells was analyzed using reverse-transcription polymerase chain reaction specific for TLRs and by flow cytometry using anti-TLR2, -TLR4, -CD4, -CD8, and -CD11c antibodies. These measurements were compared with the locoregional response of OK-432 immunotherapy for malignant ascites, as well as TNF-α producing potential, which was measured by ELISA, of ascites cells stimulated in vitro with OK-432. It was observed that OK-432 immunotherapy for malignant ascites showed 8 positive (67%) and 4 negative responses with the tolerable adverse effects of fever elevation and abdominal pain. The TNF-α production of ascites cells by in vitro OK-432 stimulation was significantly higher in responder patients than in non-responders. The clinical responses were correlated with the expression of the TLR4 gene of ascites cells. The TNF-α-producing potential of ascites cells by in vitro OK-432 stimulation was dependent on the existence of a CD11c+TLR-4+ cell population in ascites cells. OK-432 was highly stimulatory for TNF-α production of ascites cells compared with other biological response modifiers of PSK and LEM. These results suggest that TLR-4 expression on ascites cells of a macrophage lineage is essential for ascites cells to produce TNF-α in relation to OK-432 stimulation and for subsequent positive clinical responses in locoregional immunotherapy using OK-432 for malignant ascites from gastric cancer.
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The involvement of TLRs in the action mechanism of OK-432, a bacterial preparation, was investigated in the locoregional treatment of malignant ascites from gastric cancer. The expression of TLRs in ascites cells was analyzed using reverse-transcription polymerase chain reaction specific for TLRs and by flow cytometry using anti-TLR2, -TLR4, -CD4, -CD8, and -CD11c antibodies. These measurements were compared with the locoregional response of OK-432 immunotherapy for malignant ascites, as well as TNF-α producing potential, which was measured by ELISA, of ascites cells stimulated in vitro with OK-432. It was observed that OK-432 immunotherapy for malignant ascites showed 8 positive (67%) and 4 negative responses with the tolerable adverse effects of fever elevation and abdominal pain. The TNF-α production of ascites cells by in vitro OK-432 stimulation was significantly higher in responder patients than in non-responders. 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The clinical responses were correlated with the expression of the TLR4 gene of ascites cells. The TNF-α-producing potential of ascites cells by in vitro OK-432 stimulation was dependent on the existence of a CD11c+TLR-4+ cell population in ascites cells. OK-432 was highly stimulatory for TNF-α production of ascites cells compared with other biological response modifiers of PSK and LEM. 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source MEDLINE; EZB-FREE-00999 freely available EZB journals
subjects Ascites - metabolism
Ascites - therapy
Base Sequence
Biological and medical sciences
CD11c Antigen - metabolism
DNA Primers
Flow Cytometry
Humans
Immunotherapy
Medical sciences
Picibanil - therapeutic use
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Stomach Neoplasms - metabolism
Stomach Neoplasms - therapy
Toll-Like Receptor 4 - genetics
Toll-Like Receptor 4 - metabolism
Tumor Necrosis Factor-alpha - biosynthesis
Tumors
title Essential Requirement of Toll-like Receptor 4 Expression on CD11c+ Cells for Locoregional Immunotherapy of Malignant Ascites Using a Streptococcal Preparation OK-432
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