Reference - Detail
| RRC ID | 86326 |
|---|---|
| Author | Chen YH, Lee YM, Ou DL, Hsu CL, Hsu C, Chen CN, Ko JY, Tan CT. |
| Title | Regorafenib enhances M1/M2 macrophage polarization by inhibiting the secretion of plasminogen activator inhibitor-1 in head and neck squamous cell carcinoma. |
| Journal | Life Sci |
| Abstract |
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. |
| Volume | 358 |
| Pages | 123147 |
| Published | 2024-12-1 |
| DOI | 10.1016/j.lfs.2024.123147 |
| PII | S0024-3205(24)00737-9 |
| PMID | 39419267 |
| MeSH | Animals Cell Line, Tumor Cell Proliferation / drug effects Head and Neck Neoplasms* / drug therapy Head and Neck Neoplasms* / metabolism Head and Neck Neoplasms* / pathology Humans Macrophages* / drug effects Macrophages* / metabolism Mice Mice, Inbred C57BL Phenylurea Compounds* / pharmacology Plasminogen Activator Inhibitor 1* / metabolism Pyridines* / pharmacology Squamous Cell Carcinoma of Head and Neck* / drug therapy Squamous Cell Carcinoma of Head and Neck* / metabolism Squamous Cell Carcinoma of Head and Neck* / pathology Tumor Microenvironment / drug effects |
| IF | 3.647 |
| Resource | |
| Human and Animal Cells | Sq-1979(RCB0284) |