Laricitrin ameliorates lung cancer-mediated dendritic cell suppression by inhibiting signal transducer and activator of transcription 3.
Natural polyphenolic compounds of grapes and their seeds are thought to be therapeutic adjuvants in a variety of diseases, including cancer prevention. This study was carried out to investigate the effect of grape phenolic compounds on the regulation of cancer-mediated immune suppression. Laricitrin exhibits the greatest potential to ameliorate the suppressive effects of lung cancer on dendritic cells' (DCs') differentiation, maturation and function. Human lung cancer A549 and CL1-5 cells change the phenotype of DCs that express to high levels of IL-10 and prime T cells towards an immune suppression type-2 response (Th2). Laricitrin treatment stimulated DC differentiation and maturation in the condition media of cancer cells, a finding supported by monocyte marker CD14's disappearance and DC marker CD1a's upregulation. Laricitrin decreases expression of IL-10 in cancer-conditioned DCs, and subsequently switches CD4+ T cell response from Th2 to Th1 in vitro and in vivo. Reversal of laricitrin on lung cancer-induced DCs' paralysis was via inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Laricitrin also potentiated the anticancer activity of cisplatin in mouse models. Thus, laricitrin could be an efficacious immunoadjuvant and have a synergistic effect when combined with chemotherapy.
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Wei-An
WA
Chang
Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Jen-Yu
JY
Hung
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Shu-Fang
SF
Jian
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yi-Shiuan
YS
Lin
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Cheng-Ying
CY
Wu
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ya-Ling
YL
Hsu
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Po-Lin
PL
Kuo
D000276:Adjuvants, Immunologic; D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004357:Drug Synergism; D005419:Flavonoids / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D010636:Phenols / Q000627:therapeutic use*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D018417:Th1 Cells / Q000276:immunology*; D059016:Tumor Microenvironment; D027843:Vitis; D023041:Xenograft Model Antitumor Assays
D000276:Adjuvants, Immunologic; D018949:Antigens, CD1; C419393:CD1a antigen; D005419:Flavonoids; D010636:Phenols; D050796:STAT3 Transcription Factor; C000626329:laricitrin; D016753:Interleukin-10; C040015:myricetin; D002945:Cisplatin
IL-10; STAT3; dendritic cell; laricitrin; lung cancer