Lu et al. showed a correlation between high tumor expression of IL-20 (which correlated with high PD-L1) and poor survival of patients with pancreatic cancer (PDAC). Specimens from orthotopic and spontaneous-transgenic PDAC mouse models expressed IL-20 and its receptors. IL-20R1-knockdown tumor cells had reduced growth, and anti-IL-20 antibody (7E) therapy slowed tumor growth, extended host survival, and reduced IL-20, PD-L1, and fibrosis and M2 macrophage marker expression. 7E and anti-PD-1 co-therapy more effectively inhibited tumor growth than monotherapy. 7E reduced adipose tissue lipolysis, but not muscle wasting in cancer-cachexia models.
Contributed by Paula Hochman
ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) and cancer-associated cachexia (CAC) are multifactorial and characterized by dysregulated inflammatory networks. Whether the proinflammatory cytokine IL-20 is involved in the complex networks of PDAC and CAC remains unclear. Here, we report that elevated IL-20 levels in tumor tissue correlate with poor overall survival in 72 patients with PDAC. In vivo, we establish a transgenic mouse model (KPC) and an orthotopic PDAC model and examine the therapeutic efficacy of an anti-IL-20 monoclonal antibody (7E). Targeting IL-20 not only prolongs survival and attenuates PD-L1 expression in both murine models but also inhibits tumor growth and mitigates M2-like polarization in the orthotopic PDAC model. Combination treatment with 7E and an anti-PD-1 antibody shows better efficacy in inhibiting tumor growth than either treatment alone in the orthotopic PDAC model. Finally, 7E mitigates cachexic symptoms in CAC models. Together, we conclude IL-20 is a critical mediator in PDAC progression.
Author Info: (1) Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. (2) Department of Biochemistry and Molecular Biology, College of Medic
Author Info: (1) Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. (2) Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. (3) Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. (4) Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. (5) Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. (6) Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. (7) Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. mingshi.chang@gmail.com. Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. mingshi.chang@gmail.com.
