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  • American Association for Cancer Research (AACR)  (3)
  • 1
    Online Resource
    Online Resource
    Abstract 5201: Enhanced production of IL-2 from anti CD3-stimulated mouse spleen cells by artepillin C, a major component of Brazilian green propolis
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. 5201-5201
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 5201-5201
    Abstract: Objectives: It has been reported that Brazilian green propolis (BGP) possesses anti-tumor and chemo-preventive properties against prostate cancer (Szliszaka E, 2011). And bioactive components from propolis have been shown to have anti-cancerous effects upon hepatocellular carcinoma (Liu X, 2021). These observations revealed that propolis can be an anti-cancer drugs, however the immunological effects upon tumor microenvironments of these naturally occurring components has not been elucidated. In this report, we attempt to clarify immune modulatory effects of BGP and the major component, artepillin C, by observing cytokine production from activated T cells. Methods: The mouse spleen cell stimulated by anti-CD3 monoclonal antibody were co-cultured with BGP, artepillin C and HC030031, an antagonist of TRPA1 Ca2+ channel. The productions of IFN-γ, IL-6, IL-17, IL-4, IL-10 and IL-2 was assayed by ELISA. Results: Our results demonstrated the production of IL-2 was markedly enhanced, while the production of IL-4 and IL-10 was not significantly affected; by contrast, the production of IFN-γ, IL-6 and IL-17 were markedly reduced, in the highly viable stimulated spleen cells treated with BGP. These effects were also reproduced in the cells treated with artepillin C, a major component of BGP. The enhancement of IL-2 production by artepillin C was significantly alleviated by adding 10 HC030031, an antagonist of TRPA1 Ca2+ channel, suggesting the enhancement of the cytokine production by artepillin C could be mediated by Ca2+ influx. Conclusions: The artepillin C, a major component of BGP, is an important regulator of activated T lymphocytes and specifically augmented the expression of IL-2 vie Ca2+-permeable cation channel, TRPA1. These effects may exert immunomodulatory effects upon tumor microenvironments. Citation Format: Nobuo Kondoh, Masako Kamiya, Hanemi Tsuruta, Moe Takahashi, Kumiko Ikeno, Kyohei Ueno, Naoki Umemura, Eiji Takayama, Harumi Kawaki, Genjiro Nakamura, Toru Nikaido, Yasunori Muramatsu, Megumi Ando. Enhanced production of IL-2 from anti CD3-stimulated mouse spleen cells by artepillin C, a major component of Brazilian green propolis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5201.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2022-5201
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 2
    Online Resource
    Online Resource
    Induction of PD-L1 Expression by the EML4–ALK Oncoprotein and Downstream Signaling Pathways in Non–Small Cell Lung Cancer
    American Association for Cancer Research (AACR) ; 2015
    In:  Clinical Cancer Research Vol. 21, No. 17 ( 2015-09-01), p. 4014-4021
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 21, No. 17 ( 2015-09-01), p. 4014-4021
    Abstract: Purpose: Therapies targeted to the immune checkpoint mediated by PD-1 and PD-L1 show antitumor activity in a subset of patients with non–small cell lung cancer (NSCLC). We have now examined PD-L1 expression and its regulation in NSCLC positive for the EML4–ALK fusion gene. Experimental Design: The expression of PD-L1 at the protein and mRNA levels in NSCLC cell lines was examined by flow cytometry and by reverse transcription and real-time PCR analysis, respectively. The expression of PD-L1 in 134 surgically resected NSCLC specimens was evaluated by immunohistochemical analysis. Results: The PD-L1 expression level was higher in NSCLC cell lines positive for EML4–ALK than in those negative for the fusion gene. Forced expression of EML4–ALK in Ba/F3 cells markedly increased PD-L1 expression, whereas endogenous PD-L1 expression in EML4–ALK–positive NSCLC cells was attenuated by treatment with the specific ALK inhibitor alectinib or by RNAi with ALK siRNAs. Furthermore, expression of PD-L1 was downregulated by inhibitors of the MEK–ERK and PI3K–AKT signaling pathways in NSCLC cells positive for either EML4–ALK or activating mutations of the EGFR. Finally, the expression level of PD-L1 was positively associated with the presence of EML4–ALK in NSCLC specimens. Conclusions: Our findings that both EML4–ALK and mutant EGFR upregulate PD-L1 by activating PI3K–AKT and MEK–ERK signaling pathways in NSCLC reveal a direct link between oncogenic drivers and PD-L1 expression. Clin Cancer Res; 21(17); 4014–21. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-15-0016
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 3
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    Online Resource
    Abstract 1910: Augmented secretion of IL-1α from mouse oral squamous cell carcinoma (OSCC) cells caused by the serum deprivation and hypoxia promotes immune-suppressive activity of mesenchymal stromal cells
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. 1910-1910
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 1910-1910
    Abstract: Objectives; We have already reported that mouse oral squamous carcinoma (OSCC), Sq-1979-1, cells produce IL-1α which specifically enhances the immunosuppressive activity of co-cultured mesenchymal stromal, 10T1/2, cells (Morimoto-Ito, Open Dent J. 2019). In this report, we evaluated conditions promoting the expression of IL-1α of Sq-1979-1 cells to further enhance immunosuppressive function of the 10T1/2 cells, and also examined the expression in OSCC tissues. Methods; Expression of IL-1α in Sq-1979-1 cells was evaluated by RT-PCR, western blots and enzyme-linked immune sorbent assay (ELISA). Conditioned mediums (CMs) from Sq-1979-1 cells were co-cultured with 10T1/2 cells and anti-CD3 antibody-stimulated mouse spleen cells. The production of interferon (IFN)- γ and IL-1α was evaluated using ELISA. The function of IL-1α in CM was examined by anti- IL-1α antibody. Immunohistochemical analysis of OSCC tissues was performed. Results; The production of IL-1α from Sq-1979-1 cells was specifically enhanced in lower serum (0.5% or 1.0%FBS), or under hypoxia (1.0% oxygen) compared to that in the standard growth condition supplemented with 10% FBS under normoxia. Compared to standard CM, the CMs prepared in 0.5% and 1.0% FBS, or under hypoxia significantly reduced IFN-γ production from stimulated spleen cells co-cultured with 10T1/2 cells. These functions of the CMs completely abolished by anti- IL-1α antibody. Expression of IL-1α in OSCC tissues was prominent in the midst of carcinomatous cellular lesion, or nearby necrotic lesion, where the supply deficiency could be occurred. Conclusions; The promotion of immunosuppressive activity of mesenchymal cells by Sq-1979-1 cells was specifically augmented in lower serum and hypoxic conditions, mediated by increased IL-1α production. Citation Format: Nobuo Kondoh, Akihiro Matsunami, Masako Mizuno-Kamiya, Naoki Umemura, Eiji Takayama, Harumi Kawaki, Kyouhei Ueno, Hiroe Morimoto-Ito, Yasunori Muramatsu, Shinichiro Sumitomo. Augmented secretion of IL-1α from mouse oral squamous cell carcinoma (OSCC) cells caused by the serum deprivation and hypoxia promotes immune-suppressive activity of mesenchymal stromal cells [abstract] . In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1910.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2021-1910
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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