Combination therapy with liposomal doxorubicin and liposomal vaccine containing E75, an HER-2/neu-derived peptide, reduces myeloid-derived suppressor cells and improved tumor therapy.
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ID: 103312
2020
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Abstract
Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells causing resistance to immunotherapies in cancer tumors. In the current study, various immunogenic and therapeutic features of the combination therapies with non-liposomal Doxorubicin (Dox) and the E75 immunogenic peptide (Pep), derived from the human epidermal receptor-2 (HER-2), are investigated in parallel with their liposomal formulations (Lip-Dox (Doxil®) and Lip-Pep). Therefore, triple injection doses of Lip-Pep were preceded with Dox and Lip-Dox injections in TUBO/breast tumor-bearing BALB/c mice. Chemotherapy with either Dox or Lip-Dox reduced the frequency of MDSCs, the level of reactive oxygen species (ROS), and MDSCs-associated genes of Arg1, iNOS, S100A8, S100A9. Whereas Lip-Pep + Dox and Lip-Pep + Lip-Dox treatments synergistically potentiated the immunized splenocytes to produce INF-γ and enhanced the frequency of the anti-tumor CD8 and CD4 T cells as opposed to both chemotherapy and immunotherapy regimens. Chemo-immunotherapy increased the number of tumor-infiltrating lymphocytes (TILs) and reduced the level of CD25 FoxP3 T regulatory cells. Taken together, chemo-immunotherapy was the optimum treatment for the limitation of tumor progression as they targeted more cancer-related immune players.
| Reference Key |
zamani2020combinationlife
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| Authors | Zamani, Parvin;Navashenaq, Jamshid Gholizadeh;Teymouri, Manouchehr;Karimi, Maryam;Mashreghi, Mohammad;Jaafari, Mahmoud Reza; |
| Journal | Life sciences |
| Year | 2020 |
| DOI |
S0024-3205(20)30394-5
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