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.
Recently scientists from Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan report that elevated IL-20 levels in tumor tissue correlate with poor overall survival in 72 patients with PDAC.
In vivo, they 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.
IL-20 was correlated with PD-L1 level and survival in patients
They performed immunohistochemical (IHC) staining to analyze the expression of IL-20 in tumor tissue samples from 72 patients with PDAC. IL-20 was strongly expressed in tumor cells and neoplastic ductal epithelial cells (Fig. 1a; left panel) but only lowly expressed by ductal epithelial cells in nontumorous pancreatic tissue (Fig. 1a; right panel). IL-20 expression was remarkably correlated with overall survival, and relatively high IL-20 expression predicted poor survival (Fig. 1b; left panel). There was a significantly negative correlation between high expression of IL-20 and survival in patients with advanced-stage PDAC (Fig. 1b; right panel). PD-L1 is highly expressed in PDAC and plays an important role in tumor progression. Thus we stained the 72 tumor tissue samples with an anti-PD-L1 antibody and compared the expression of IL-20 and PD-L1 in these patients. PD-L1 was expressed in the patients with PDAC (Fig. 1c), and IL-20 was significantly correlated with PD-L1 expression (r = 0.6203, p < 0.0001; Fig. 1d).
In conclusion, they demonstrated that IL-20 played pivotal roles in PDAC and that the anti-IL-20 antibody 7E retarded tumor progression, inhibited fibrosis in the pancreas, downregulated PD-L1 expression, mitigated CAC, and synergized with anti-PD-1 therapy to inhibit tumor growth. Therefore, the anti-IL-20 antibody is a potential therapeutic for PDAC. This research has been published on Nature in September 2020.
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