Regorafenib enhances M1/M2 macrophage polarization by inhibiting the secretion of plasminogen activator inhibitor-1 in head and neck squamous cell carcinoma.

Autor: Chen YH; Department of Otolaryngology, National Taiwan University Hospital, Taipei 10051, Taiwan; Stem Cell Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei 10051, Taiwan; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 10051, Taiwan., Lee YM; Department of Otolaryngology, National Taiwan University Hospital, Taipei 10051, Taiwan; Stem Cell Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei 10051, Taiwan., Ou DL; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 10051, Taiwan; YongLin Institute of Health, National Taiwan University, Taipei 10051, Taiwan., Hsu CL; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 10051, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei 10051, Taiwan., Hsu C; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 10051, Taiwan; Department of Oncology, National Taiwan University Cancer Center, Taipei 10672, Taiwan; Department of Oncology, National Taiwan University Hospital, Taipei 10051, Taiwan., Chen CN; Department of Otolaryngology, National Taiwan University Hospital, Taipei 10051, Taiwan., Ko JY; Department of Otolaryngology, National Taiwan University Hospital, Taipei 10051, Taiwan., Tan CT; Department of Otolaryngology, National Taiwan University Hospital, Taipei 10051, Taiwan; Stem Cell Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei 10051, Taiwan; Department of Otolaryngology, National Taiwan University College of Medicine, Taipei 10051, Taiwan; Department of Otolaryngology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu 302058, Taiwan. Electronic address: tanct5222@ntu.edu.tw.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2024 Dec 01; Vol. 358, pp. 123147. Date of Electronic Publication: 2024 Oct 15.
DOI: 10.1016/j.lfs.2024.123147
Abstrakt: Aims: Regorafenib, an oral multikinase inhibitor, is approved for the treatment of various metastatic/advanced cancers. Although clinical trials have reported the efficacy of regorafenib in multiple cancer types, its immunomodulatory activity in head and neck squamous cell carcinoma (HNSCC) remains unclear.
Main Methods: This study investigated the effects of regorafenib on tumorigenesis by using two mouse models of HNSCC. The distribution of immune cells in tumor tissues was assessed through flow cytometry, RNA sequencing, and multiplex immunofluorescence staining.
Key Findings: Regorafenib exhibited significant antitumor activity in our HNSCC mouse models. Tumor-infiltrating lymphocyte isolation and RNA sequencing revealed that regorafenib can activate immune functions. Moreover, regorafenib-treated tumor-conditioned medium regulated macrophage proliferation ex vivo. Our data suggests that regorafenib modulates immune function by regulating both tumor and immune cells. Specifically, regorafenib induced the polarization of macrophages toward the proinflammatory M1 phenotype by suppressing the production of plasminogen activator inhibitor 1 (PAI-1), a macrophage regulator. In addition, regorafenib suppressed the secretion of PAI-1 from ex vivo human HNSCC organoids.
Significance: Regorafenib enhances M1/M2 macrophage polarization and suppresses PAI-1 secretion from cancer cells, leading to a shift from M2 to M1 macrophages in the HNSCC tumor microenvironment.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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