Success and failure of dendritic cell (DC) anticancer activity may be modulated by nitric oxide synthetase (NOS) gene expression: a hypothesis.
Observations during the last several years on the relationships between bone marrow-derived dendritic cells (DC) and the cells which are in direct contact with them led to the idea that DC may have regulatory properties. Such regulatory properties exerted by DC were noted in experimental cancers in murine systems as well as in human cancers. It was noted that patients with the same type of cancer in which DC are present in the tumor survive longer than patients without DC in the tumor. It is not known how DC can abrogate the development of the metastatic tumor cells in the primary tumor, nor how the tumor cells are capable of abrogating the anticancer activity of the DC and allowing the development of tumor metastases. Studies on the anticancer activity of macrophages revealed that these cells have an inducible Nitric Oxide (NO) synthase (NOS) which utilizes arginine to produce NO. Suppressor macrophages release NO, which inhibits the ribonucleotide reductase and mitochondrial oxidation in tumor cells in vitro. It was also reported (4) that Interferon gamma (IFN-gamma), produced by murine T helper 1 cells, induces NOS activity in macrophages, while T helper 2 cells which produce Interleukin-4 (IL-4) inhibit the expression of NOS in macrophages. The hypothesis presented in this paper suggests that DC have a gene for NOS which is inducible by immunomodulators (e.g. IFN gamma, OK432, LPS) and can be suppressed by cytokines produced by tumor cells (e.g. IL-4, IL-10).(ABSTRACT TRUNCATED AT 250 WORDS)
Becker
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Department of Molecular Virology, Faculty of Medicine, Hebrew University of Jerusalem, Israel.
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics*; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D008214:Lymphocytes / Q000166:cytology; D008264:Macrophages / Q000201:enzymology; D009369:Neoplasms / Q000235:genetics / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases