title: Cucurbitacin B regulates immature myeloid cell differentiation and enhances antitumor immunity in patients with lung cancer.
abstract: The aberrant activation of the JAK2/STAT3 signaling in immature myeloid dendritic cells (DCs) is associated with immune tolerance and poor antitumor immunity. The objective of this study was to test the hypothesis that Cucurbitacin B (CuB), a selective inhibitor of JAK2/STAT3 signaling, could promote DC differentiation and improve antitumor immunity. Twelve patients with advanced lung cancers were treated orally with CuB daily for 7 consecutive days. The frequency of peripheral blood myeloid DCs and immature myeloid cells (imCs) in those patients and healthy controls was characterized longitudinally by flow cytometry. The effect of CuB on the differentiation of DCs and p53-specific T responses was evaluated in vitro. The percentages of Lin(-)DR(-)CD33(+) imCs and Lin(-)DR(+)CD33(+) DCs were significantly different between patients with lung cancers and healthy controls (1.55% vs. 0.82%, p=0.002; 0.60% vs. 1.90%, p=0.000). Treatment with CuB significantly increased the frequency of Lin(-)DR(+)CD33(+), but reduced the frequency of Lin(-)DR(-)CD33(+) in patients with lung cancers (p<0.05). Treatment with CuB induced the differentiation of DCs cocultured with tumor cells 16HBE/BPDE and enhanced the sensitivity of 16HBE/BPDE cells to p53-specific CTL by inhibiting the JAK2/STAT3 activation, but also enhancing the interferon-γ-related STAT1 activation in 16HBE/BPDE cells. CuB significantly reduced the frequency of imCs in patients with lung cancers and enhanced the effect of p53-specific CTL on tumor 16HBE/BPDE cells.
authors: Institute of Respiratory Disease, the First Affiliated Hospital, Guangzhou Medical College, Guangzhou, China. lvping75@163.com
authors: Ping
authors: P
authors: Lu
authors: Baodan
authors: B
authors: Yu
authors: Jun
authors: J
authors: Xu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology*; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D014315:Triterpenes / Q000627:therapeutic use*
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014315:Triterpenes; C041246:cucurbitacin B; C507924:JAK2 protein, human; D053614:Janus Kinase 2