The Soluble Factor from Oral Cancer Cell Lines Inhibits Interferon-γ Production by OK-432 via the CD40/CD40 Ligand Pathway

Autor:	Yasusei Kudo, Naito Kurio, Keiko Kudoh, Go Ohe, Yasuhiro Mouri, Kumiko Kamada, Youji Miyamoto, Natsumi Takamaru
Rok vydání:	2021
Předmět:	0301 basic medicine Cancer Research medicine.medical_treatment medicine.disease_cause Peripheral blood mononuclear cell Article 03 medical and health sciences 0302 clinical medicine interferon-γ CD40 medicine Cytotoxic T cell Neutralizing antibody RC254-282 biology Chemistry Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cancer hemic and immune systems Immunotherapy oral cancer medicine.disease Molecular biology conditioned medium 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell Streptococcus pyogenes OK-432 biology.protein
Zdroj:	Cancers Volume 13 Issue 13 Cancers, Vol 13, Iss 3301, p 3301 (2021)
ISSN:	2072-6694
Popis:	OK-432 is a potent immunotherapy agent for several types of cancer, including oral cancer. We previously reported that OK-432 treatment can induce the production of high levels of IFN-γ from peripheral blood mononuclear cells (PBMCs). Moreover, the IFN-γ production from PBMCs by OK-432 is impaired by conditioned media (CM) from oral cancer cells. To determine the inhibitory mechanism of IFN-γ production by CM, the genes involved in IFN-γ production was retrieved by cDNA microarray analysis. We found that CD40 played a key role in IFN-γ production via IL-12 production. Although the expression levels of CD40 were upregulated by OK-432 treatment in PBMCs, CM inhibited OK-432-induced CD40 expression. These findings suggest that uncertain soluble factor(s) in CM may suppress IFN-γ production via the CD40/CD40L–IL-12 axis in PBMCs. (1) Background: OK-432 is a penicillin-killed, lyophilized formulation of a low-toxicity strain (Su) of Streptococcus pyogenes (Group A). It is a potent immunotherapy agent for several types of cancer, including oral cancer. We previously showed that (i) OK-432 treatment induces a high amount of IFN-γ production from peripheral blood mononuclear cells (PBMCs), and (ii) conditioned medium (CM) from oral cancer cells suppresses both the IFN-γ production and cytotoxic activity of PBMCs driven by OK-432. The aim of this study was to determine the inhibitory mechanism of OK-432-induced IFN-γ production from PBMCs by CM. (2) Methods: We performed cDNA microarray analysis, quantitative RT-PCR, and ELISA to reveal the inhibitory mechanism of CM. (3) Results: We found that CD40 plays a key role in IFN-γ production via IL-12 production. Although OK-432 treatment upregulated the expression levels of the IL-12p40, p35, and CD40 genes, CM from oral cancer cells downregulate these genes. The amount of IFN-γ production by OK-432 treatment was decreased by an anti-CD40 neutralizing antibody. (4) Conclusions: Our study suggests that uncertain soluble factor(s) produced from oral cancer cells may inhibit IFN-γ production from PBMCs via suppressing the CD40/CD40L–IL-12 axis.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4f3dfb93376f728b06558f8ae498bc3c https://doi.org/10.3390/cancers13133301 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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