IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models

Shao-Wei Lu, Hong-Chin Pan, Yu-Hsiang Hsu, Kung-Chao Chang, Li-Wha Wu, Wei-Yu Chen and Ming-Shi Chang ()
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Shao-Wei Lu: National Cheng Kung University
Hong-Chin Pan: National Cheng Kung University
Yu-Hsiang Hsu: National Cheng Kung University
Kung-Chao Chang: National Cheng Kung University
Li-Wha Wu: National Cheng Kung University
Wei-Yu Chen: Kaohsiung Chang Gung Memorial Hospital
Ming-Shi Chang: National Cheng Kung University

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18244-8

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