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NLRP3 Deficiency in Hepatocellular Carcinoma Enhances Surveillance of NK-92 through a Modulation of MICA/B.
Lee, Hwan Hee; Kim, Dongoh; Jung, Joohee; Kang, Hyojeung; Cho, Hyosun.
Afiliação
  • Lee HH; Department of Pharmacy, Duksung Women's University, Seoul 01369, Korea.
  • Kim D; Duksung Innovative Drug Center, Duksung Women's University, Seoul 01369, Korea.
  • Jung J; Duksung Innovative Drug Center, Duksung Women's University, Seoul 01369, Korea.
  • Kang H; Department of Pharmacy, Duksung Women's University, Seoul 01369, Korea.
  • Cho H; Duksung Innovative Drug Center, Duksung Women's University, Seoul 01369, Korea.
Int J Mol Sci ; 22(17)2021 Aug 27.
Article em En | MEDLINE | ID: mdl-34502191
ABSTRACT
Human hepatocellular carcinoma (HCC) is the most common and even worse at prognosis. The patients with HCC which accompanied by other diseases, such as cirrhosis, can be limited in various treatments, such as chemotherapy, not HCC patients without other diseases. NLRP3 inflammasome plays an important role in the innate immune response, but emerging evidence has indicated that the NLRP3 inflammasome is implicated in all stages of cancer development. Various cells express NLRP3 protein through the autocrine or paracrine signaling in their environment, but NK cells do not. The expanding evidence shows that patients who suffer from liver cancers have a low frequency of natural killer (NK) cells, and the function of these cells is also impaired. Thus, we examined how the expression of NLRP3 in HCC cells affects cancer surveillance by NK cells in a state of a co-culture of both cells. When the expression of NLRP3 in HCC cells was ablated, MICA/B on the surface of HCC cells was upregulated through the lowered expression of matrix metalloproteinase. The expression of MICA on the surface of HCC cells interacted with the NKG2D receptor on NK-92 cells, which led to NK cytotoxicity. Furthermore, in a xenograft mice model, NLRP3 KO HCC cells delayed tumor development and metastasis as well as increased the sensitivity to NK cell cytotoxicity. Taken together, NLRP3 KO in HCC could enhance NK immunosurveillance through an interaction of NKG2D-MICA.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Matadoras Naturais / Antígenos de Histocompatibilidade Classe I / Monitorização Imunológica / Carcinoma Hepatocelular / Citotoxicidade Imunológica / Proteína 3 que Contém Domínio de Pirina da Família NLR Tipo de estudo: Screening_studies Limite: Animals / Female / Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Matadoras Naturais / Antígenos de Histocompatibilidade Classe I / Monitorização Imunológica / Carcinoma Hepatocelular / Citotoxicidade Imunológica / Proteína 3 que Contém Domínio de Pirina da Família NLR Tipo de estudo: Screening_studies Limite: Animals / Female / Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2021 Tipo de documento: Article