Frontiers in Immunology (May 2023)
Repurposing pentamidine for cancer immunotherapy by targeting the PD1/PD-L1 immune checkpoint
- Tingxuan Gu,
- Tingxuan Gu,
- Xueli Tian,
- Xueli Tian,
- Yuanyuan Wang,
- Yuanyuan Wang,
- Wenqian Yang,
- Wenqian Yang,
- Wenwen Li,
- Mengqiu Song,
- Mengqiu Song,
- Ran Zhao,
- Ran Zhao,
- Mengqiao Wang,
- Mengqiao Wang,
- Quanli Gao,
- Tiepeng Li,
- Chengjuan Zhang,
- Joydeb Kumar Kundu,
- Kangdong Liu,
- Kangdong Liu,
- Kangdong Liu,
- Zigang Dong,
- Zigang Dong,
- Mee-Hyun Lee,
- Mee-Hyun Lee,
- Mee-Hyun Lee,
- Mee-Hyun Lee
Affiliations
- Tingxuan Gu
- Department of Pathophysiology, School of Basic Medical Sciences, Academy of Medical Science, College of Medicine, Zhengzhou University, Zhengzhou, China
- Tingxuan Gu
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Xueli Tian
- Department of Pathophysiology, School of Basic Medical Sciences, Academy of Medical Science, College of Medicine, Zhengzhou University, Zhengzhou, China
- Xueli Tian
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Yuanyuan Wang
- Department of Pathophysiology, School of Basic Medical Sciences, Academy of Medical Science, College of Medicine, Zhengzhou University, Zhengzhou, China
- Yuanyuan Wang
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Wenqian Yang
- Department of Pathophysiology, School of Basic Medical Sciences, Academy of Medical Science, College of Medicine, Zhengzhou University, Zhengzhou, China
- Wenqian Yang
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Wenwen Li
- Department of Pathophysiology, School of Basic Medical Sciences, Academy of Medical Science, College of Medicine, Zhengzhou University, Zhengzhou, China
- Mengqiu Song
- Department of Pathophysiology, School of Basic Medical Sciences, Academy of Medical Science, College of Medicine, Zhengzhou University, Zhengzhou, China
- Mengqiu Song
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Ran Zhao
- Department of Pathophysiology, School of Basic Medical Sciences, Academy of Medical Science, College of Medicine, Zhengzhou University, Zhengzhou, China
- Ran Zhao
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Mengqiao Wang
- Department of Pathophysiology, School of Basic Medical Sciences, Academy of Medical Science, College of Medicine, Zhengzhou University, Zhengzhou, China
- Mengqiao Wang
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Quanli Gao
- Department of Immunology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
- Tiepeng Li
- Department of Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
- Chengjuan Zhang
- Department of Immunology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
- Joydeb Kumar Kundu
- Li Ka Shing Applied Virology Institute, University of Alberta, Edmonton, AB, Canada
- Kangdong Liu
- Department of Pathophysiology, School of Basic Medical Sciences, Academy of Medical Science, College of Medicine, Zhengzhou University, Zhengzhou, China
- Kangdong Liu
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Kangdong Liu
- Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, China
- Zigang Dong
- Department of Pathophysiology, School of Basic Medical Sciences, Academy of Medical Science, College of Medicine, Zhengzhou University, Zhengzhou, China
- Zigang Dong
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Mee-Hyun Lee
- Department of Pathophysiology, School of Basic Medical Sciences, Academy of Medical Science, College of Medicine, Zhengzhou University, Zhengzhou, China
- Mee-Hyun Lee
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Mee-Hyun Lee
- Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, China
- Mee-Hyun Lee
- College of Korean Medicine, Dongshin University, Naju, Republic of Korea
- DOI
- https://doi.org/10.3389/fimmu.2023.1145028
- Journal volume & issue
-
Vol. 14
Abstract
Immunotherapy has emerged as an effective therapeutic approach to several cancer types. The reinvigoration of tumor-infiltrating lymphocyte-mediated immune responses via the blockade of immune checkpoint markers, such as program cell death-1 (PD-1) or its cognate ligand PD-L1, has been the basis for developing clinically effective anticancer therapies. We identified pentamidine, an FDA-approved antimicrobial agent, as a small-molecule antagonist of PD-L1. Pentamidine enhanced T-cell-mediated cytotoxicity against various cancer cells in vitro by increasing the secretion of IFN-γ, TNF-α, perforin, and granzyme B in the culture medium. Pentamidine promoted T-cell activation by blocking the PD-1/PD-L1 interaction. In vivo administration of pentamidine attenuated the tumor growth and prolonged the survival of tumor-bearing mice in PD-L1 humanized murine tumor cell allograft models. Histological analysis of tumor tissues showed an increased number of tumor-infiltrating lymphocytes in tissues derived from pentamidine-treated mice. In summary, our study suggests that pentamidine holds the potential to be repurposed as a novel PD-L1 antagonist that may overcome the limitations of monoclonal antibody therapy and can emerge as a small molecule cancer immunotherapy.
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