Doxil chemotherapy plus liposomal P5 immunotherapy decreased myeloid-derived suppressor cells in murine model of breast cancer

Nanomedicine. 2020 Feb:24:102150. doi: 10.1016/j.nano.2020.102150. Epub 2020 Jan 10.

Abstract

Myeloid-derived suppressor cells (MDSCs) play a pivotal role in cancer. To overcome the problem of the MDSCs in the tumor microenvironment in this study, a combination of immunotherapy and chemotherapy was used. For this purpose, a liposomal formulation of P5 peptide and PEGylated liposomal doxorubicin (Doxil®) was utilized to treat mice bearing HER2+ tumor model. The results revealed that Doxil® administration before immunotherapy had not only reduced the population and functions of the MDSCs in the spleen (P < 0.001) and the tumor microenvironment (P < 0.05) but had also supported further immunotherapy including enhanced CD4+ (P < 0.01) and CD8+ lymphocyte (P < 0.001) population and IFN-γ production (P < 0.001). This effect was also more pronounced with a liposomal P5 and Doxil® compared with free peptide and doxorubicin. In conclusion, the results demonstrated that Doxil® plus liposomal P5 could have a decreasing effect on MDSCs and tumor growth, and it could be beneficial in breast cancer treatment.

Keywords: Breast cancer; Chemoimmunotherapy; Doxil®; Liposomal HER2/neu-derived peptide; MDSC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy*
  • DNA, Complementary / chemistry
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / chemistry
  • Female
  • Flow Cytometry
  • Immunotherapy
  • Mice
  • Mice, Inbred BALB C
  • Myeloid-Derived Suppressor Cells / cytology*
  • Myeloid-Derived Suppressor Cells / metabolism*
  • Polyethylene Glycols / chemistry

Substances

  • DNA, Complementary
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin