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; Ming Shi Chang

doi:10.1038/s41467-020-18244-8

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, Ming Shi Chang

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

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.

Original language	English
Article number	4611
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-18244-8
Publication status	Published - 2020 Dec 1

All Science Journal Classification (ASJC) codes

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/s41467-020-18244-8

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@article{b2a1b4b9b3634090ac7bdc9cb1004242,

title = "IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models",

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 = "Lu, {Shao Wei} and Pan, {Hong Chin} and Hsu, {Yu Hsiang} and Chang, {Kung Chao} and Wu, {Li Wha} and Chen, {Wei Yu} and Chang, {Ming Shi}",

note = "Funding Information: This work was supported by the grant MOST 108-2320-B-006-025 from the Taiwan Ministry of Science and Technology. We are grateful for support from the Core Research Laboratory, College of Medicine, National Cheng Kung University and the technical services provided by the Bioimaging Core Facility of the National Core Facility for Biopharmaceuticals, Ministry of Science and Technology, Taiwan. We thank the Laboratory Animal Center, College of Medicine, National Cheng Kung University and Taiwan Animal Consortium for the technical support in IVIS system (Xenogen IVISR Spectrum Noninvasive Quantitative Molecular Imaging System). We are grateful to Dr. Kuen-Jer Tsai and Ya-Chun Hsiao for the services of image acquiring and analyzing from the FACS-like Tissue Cytometry in the Center of Clinical Medicine, National Cheng Kung University Hospital. We thank Dr. Yan-Shen Shen and Dr. Po-Hsien Huang from College of Medicine, National Cheng Kung University for providing the KPC mice. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

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doi = "10.1038/s41467-020-18244-8",

language = "English",

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T1 - IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models

AU - Lu, Shao Wei

AU - Pan, Hong Chin

AU - Hsu, Yu Hsiang

AU - Chang, Kung Chao

AU - Wu, Li Wha

AU - Chen, Wei Yu

AU - Chang, Ming Shi

N1 - Funding Information: This work was supported by the grant MOST 108-2320-B-006-025 from the Taiwan Ministry of Science and Technology. We are grateful for support from the Core Research Laboratory, College of Medicine, National Cheng Kung University and the technical services provided by the Bioimaging Core Facility of the National Core Facility for Biopharmaceuticals, Ministry of Science and Technology, Taiwan. We thank the Laboratory Animal Center, College of Medicine, National Cheng Kung University and Taiwan Animal Consortium for the technical support in IVIS system (Xenogen IVISR Spectrum Noninvasive Quantitative Molecular Imaging System). We are grateful to Dr. Kuen-Jer Tsai and Ya-Chun Hsiao for the services of image acquiring and analyzing from the FACS-like Tissue Cytometry in the Center of Clinical Medicine, National Cheng Kung University Hospital. We thank Dr. Yan-Shen Shen and Dr. Po-Hsien Huang from College of Medicine, National Cheng Kung University for providing the KPC mice. Publisher Copyright: © 2020, The Author(s).

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

AB - 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.

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JF - Nature Communications

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ER -

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

Abstract

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