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

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 (R)) was utilized to treat mice bearing HER2(+) tumor model. The results revealed that Doxil (R) 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-gamma production (P < 0.001). This effect was also more pronounced with a liposomal P5 and Doxil (R) compared with free peptide and doxorubicin. In conclusion, the results demonstrated that Doxil (R) plus liposomal P5 could have a decreasing effect on MDSCs and tumor growth, and it could be beneficial in breast cancer treatment. (C) 2020 Elsevier Inc. All rights reserved.