ArticleCancer immunology, immunotherapy : CII2016
The induction of human myeloid derived suppressor cells through hepatic stellate cells is dose-dependently inhibited by the tyrosine kinase inhibitors nilotinib, dasatinib and sorafenib, but not sunitinib.
Article in Cancer immunology, immunotherapy : CII, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Phase II trial with nivolumab and sorafenib in HCC identified enrichment of immunosuppressive monocytes in patients with Child-Pugh B liver dysfunction.JHEP reports : innovation in hepatology · 2026Article
- MDSC expansion during HIV infection: regulators, ART and immune reconstitution.Genes and immunity · 2024Review
- Genetically predicted Caspase 8 levels mediates the causal association between CD4+ T cell and breast cancer.Frontiers in immunology · 2024Article
- Review
- The recent progress of myeloid-derived suppressor cell and its targeted therapies in cancers.MedComm · 2023Review
- Influence of Lenvatinib on the Functional Reprogramming of Peripheral Myeloid Cells in the Context of Non-Medullary Thyroid Carcinoma.Pharmaceutics · 2023Article
- Therapeutic efficacy of lenvatinib for hepatocellular carcinoma with iso-high intensity in the hepatobiliary phase of Gd-EOB-DTPA-MRI.Molecular and clinical oncology · 2022Article
- Pharmacological modulation of myeloid-derived suppressor cells to dampen inflammation.Frontiers in immunology · 2022Review
- Myeloid-Derived Suppressor Cells in Prostate Cancer: Present Knowledge and Future Perspectives.Cells · 2021Review
- Review
- Myeloid-derived suppressor cells and the pathogenesis of human immunodeficiency virus infection.Open biology · 2021Review
- Immune Responses Following Locoregional Treatment for Hepatocellular Carcinoma: Possible Roles of Adjuvant Immunotherapy.Pharmaceutics · 2021Review
- Myeloid-Derived Suppressor Cells as Therapeutic Targets in Uterine Cervical and Endometrial Cancers.Cells · 2021Review
- Sequential Therapy for Hepatocellular Carcinoma after Failure of Atezolizumab plus Bevacizumab Combination Therapy.Liver cancer · 2021Article
- Regorafenib enhances antitumor immunity via inhibition of p38 kinase/Creb1/Klf4 axis in tumor-associated macrophages.Journal for immunotherapy of cancer · 2021Article
- Review
- The Power of Plasticity-Metabolic Regulation of Hepatic Stellate Cells.Cell metabolism · 2021Review
- Myeloid-Derived Suppressor Cells: A Multifaceted Accomplice in Tumor Progression.Frontiers in cell and developmental biology · 2021Review
- Therapies for tuberculosis and AIDS: myeloid-derived suppressor cells in focus.The Journal of clinical investigation · 2020Review
- Differential Targeting of Gr-MDSCs, T Cells and Prostate Cancer Cells by Dactolisib and Dasatinib.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased numbers of immunosuppressive myeloid derived suppressor cells (MDSCs) correlate with a poor prognosis in cancer patients. Tyrosine kinase inhibitors (TKIs) are used as standard therapy for the treatment of several neoplastic diseases. However, TKIs not only exert effects on the malignant cell clone itself but also affect immune cells. Here, we investigate the effect of TKIs on the induction of MDSCs that differentiate from mature human monocytes using a new in vitro model of MDSC induction through activated hepatic stellate cells (HSCs). We show that frequencies of monocytic CD14(+)HLA-DR(-/low) MDSCs derived from mature monocytes were significantly and dose-dependently reduced in the presence of dasatinib, nilotinib and sorafenib, whereas sunitinib had no effect. These regulatory effects were only observed when TKIs were present during the early induction phase of MDSCs through activated HSCs, whereas already differentiated MDSCs were not further influenced by TKIs. Neither the MAPK nor the NFκB pathway was modulated in MDSCs when any of the TKIs was applied. When functional analyses were performed, we found that myeloid cells treated with sorafenib, nilotinib or dasatinib, but not sunitinib, displayed decreased suppressive capacity with regard to CD8+ T cell proliferation. Our results indicate that sorafenib, nilotinib and dasatinib, but not sunitinib, decrease the HSC-mediated differentiation of monocytes into functional MDSCs. Therefore, treatment of cancer patients with these TKIs may in addition to having a direct effect on cancer cells also prevent the differentiation of monocytes into MDSCs and thereby differentially modulate the success of immunotherapeutic or other anti-cancer approaches.
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