PD-L1-directed PlGF/VEGF blockade synergizes with chemotherapy by targeting CD141+ cancer-associated fibroblasts in pancreatic cancer

Duk Ki Kim; Juhee Jeong; Dong Sun Lee; Do Young Hyeon; Geon Woo Park; Suwan Jeon; Kyung Bun Lee; Jin-Young Jang; Daehee Hwang; Ho Min Kim; Keehoon Jung

doi:10.1038/s41467-022-33991-6

Nature Communications (Oct 2022)

PD-L1-directed PlGF/VEGF blockade synergizes with chemotherapy by targeting CD141+ cancer-associated fibroblasts in pancreatic cancer

Duk Ki Kim,
Juhee Jeong,
Dong Sun Lee,
Do Young Hyeon,
Geon Woo Park,
Suwan Jeon,
Kyung Bun Lee,
Jin-Young Jang,
Daehee Hwang,
Ho Min Kim,
Keehoon Jung

Affiliations

Duk Ki Kim: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Juhee Jeong: Department of Anatomy and Cell Biology, Department of Biomedical Sciences, Seoul National University College of Medicine
Dong Sun Lee: Center for Biomolecular and Cellular Structure, Institute for Basic Science (IBS)
Do Young Hyeon: School of Biological Sciences, Seoul National University
Geon Woo Park: Department of Anatomy and Cell Biology, Department of Biomedical Sciences, Seoul National University College of Medicine
Suwan Jeon: Department of Anatomy and Cell Biology, Department of Biomedical Sciences, Seoul National University College of Medicine
Kyung Bun Lee: Department of Pathology, Seoul National University College of Medicine
Jin-Young Jang: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine
Daehee Hwang: School of Biological Sciences, Seoul National University
Ho Min Kim: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Keehoon Jung: Department of Anatomy and Cell Biology, Department of Biomedical Sciences, Seoul National University College of Medicine

DOI: https://doi.org/10.1038/s41467-022-33991-6
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 19

Abstract

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A desmoplastic stroma, enriched in cancer-associated fibroblasts (CAF), has been associated with resistance to therapy in patients with pancreatic ductal adenocarcinoma (PDAC). Here, after showing that chemotherapy promotes tumor fibrosis by increasing CAF frequency and activity, the authors develop a multi-paratopic VEGF decoy receptor for PD-L1 directed PlGF/VEGF blockade, promoting anti-fibrotic and anti-tumor effects in PDAC models.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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