Article ; Online: Targeting Inhibition of Accumulation and Function of Myeloid-Derived Suppressor Cells by Artemisinin via PI3K/AKT, mTOR, and MAPK Pathways Enhances Anti-PD-L1 Immunotherapy in Melanoma and Liver Tumors.
Journal of immunology research
2022 Volume 2022, Page(s) 2253436
Abstract: ... by polarizing M2-like tumor-promoting phenotype towards M1-like antitumor one. This switch is regulated via PI3K ... effective antimalarial drug with tumoricidal and immunoregulatory activities, is a potential option ... Despite the remarkable success and efficacy of immune checkpoint blockade (ICB) therapy ...
| Abstract | Despite the remarkable success and efficacy of immune checkpoint blockade (ICB) therapy such as anti-PD-L1 antibody in treating cancers, myeloid-derived suppressor cells (MDSCs) that lead to the formation of the protumor immunosuppressive microenvironment are one of the major contributors to ICB resistance. Therefore, inhibition of MDSC accumulation and function is critical for further enhancing the therapeutic efficacy of anti-PD-L1 antibody in a majority of cancer patients. Artemisinin (ART), the most effective antimalarial drug with tumoricidal and immunoregulatory activities, is a potential option for cancer treatment. Although ART is reported to reduce MDSC levels in 4T1 breast tumor model and improve the therapeutic efficacy of anti-PD-L1 antibody in T cell lymphoma-bearing mice, how ART influences MDSC accumulation, function, and molecular pathways as well as MDSC-mediated anti-PD-L1 resistance in melanoma or liver tumors remains unknown. Here, we reported that ART blocks the accumulation and function of MDSCs by polarizing M2-like tumor-promoting phenotype towards M1-like antitumor one. This switch is regulated via PI3K/AKT, mTOR, and MAPK signaling pathways. Targeting MDSCs by ART could significantly reduce tumor growth in various mouse models. More importantly, the ART therapy remarkably enhanced the efficacy of anti-PD-L1 immunotherapy in tumor-bearing mice through promoting antitumor T cell infiltration and proliferation. These findings indicate that ART controls the functional polarization of MDSCs and targeting MDSCs by ART provides a novel therapeutic strategy to enhance anti-PD-L1 cancer immunotherapy. |
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| MeSH term(s) | Animals ; Artemisinins/pharmacology ; Artemisinins/therapeutic use ; B7-H1 Antigen ; Immunologic Factors ; Immunotherapy ; Liver Neoplasms/drug therapy ; Melanoma ; Mice ; Myeloid-Derived Suppressor Cells ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; TOR Serine-Threonine Kinases ; Tumor Microenvironment |
| Chemical Substances | Artemisinins ; B7-H1 Antigen ; Immunologic Factors ; mTOR protein, mouse (EC 2.7.1.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) |
| Language | English |
| Publishing date | 2022-06-22 |
| Publishing country | Egypt |
| Document type | Journal Article |
| ZDB-ID | 2817541-4 |
| ISSN | 2314-7156 ; 2314-7156 |
| ISSN (online) | 2314-7156 |
| ISSN | 2314-7156 |
| DOI | 10.1155/2022/2253436 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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