Chromosome 1 open reading frame 190 promotes activation of NF-κB canonical pathway and resistance of dendritic cells to tumor-associated inhibition in vitro.
Tumor-associated dendritic cells (DCs) often induce T cell anergy or deletion and regulatory T cells instead of antitumor immunity. Although many tumor-associated Ags have been found, there is still no effective vaccine for cancer. Thus, novel rational strategies to enhance the immunogenicity of cancer-specific Ags are needed. Chromosome 1 open reading frame 190 (c1orf190), a gene that encodes a 239-aa hypothetical protein and contains multiple kinase phosphorylation sites, has a wide relationship with multiple signaling pathway molecules and can be regulated by multiple factors, such as TLR ligands. In this study, we demonstrate that c1orf190 can activate NF-κB, drive the production of cytokines, and promote the Ag-presenting function and the priming ability of DCs. Furthermore, c1orf190 can promote resistance of DCs to tumor-associated inhibition not only in the Ag-presenting function but also in the priming ability to induce Ag-specific T lymphocytes. Thus, c1orf190, an NF-κB activator, may be a candidate gene for regulating the function of DCs to resist tumor-associated factor-mediated dysfunction. We also found that c1orf190-mediated cytokine release is achieved by activating the canonical but not the noncanonical NF-κB pathway.
Department of Immunology, Nankai University School of Medicine and Key Laboratory of Bioactive Materials, Nankai University, Ministry of Education, People's Republic of China.
Zhizi
Z
Jing
Xin
X
Yuan
Jing
J
Zhang
Xin
X
Huang
Zhiqian
Z
Zhang
Jingyi
J
Liu
Miaomiao
M
Zhang
Jiangbo
J
Oyang
Yuan
Y
Zhang
Zhujun
Z
Zhang
Rongcun
R
Yang
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D002878:Chromosomes, Human, Pair 1 / Q000502:physiology*; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019281:Dimerization; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000502:physiology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000502:physiology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010766:Phosphorylation / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D015534:Trans-Activators / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D018836:Inflammation Mediators; C554819:LURAP1 protein, human; D016328:NF-kappa B; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins