Multiple tumor-derived factors are responsible for the accumulation and expansion of immune suppressing myeloid-derived suppressor cells (MDSCs) and M2-like tumor-associated macrophages (TAMs) in tumors. Here we show that treatment of tumor-bearing mice with docetaxel in combination with the phosphatidylserine (PS)-targeting antibody, 2aG4, potently suppressed the growth and progression of prostate tumors, and depleted M2-like TAMs and MDSCs and increased the presence of M1-like TAMs and mature dendritic cells in the tumors. In addition, the antibody markedly altered the cytokine balance in the tumor microenvironment from immunosuppressive to immunostimulatory. In vitro studies confirmed that 2aG4 re-polarized TAMs from an M2 to M1-like phenotype and drove MDSCs differentiating into M1-like TAMs and functional dendritic cells. These data suggest that PS is primarily responsible for expansion of MDSCs and M2-like TAMs in tumors, and that bavituximab, a PS-targeting antibody currently in cancer clinical trials, could reverse this process and reactive anti-tumor immunity.
- Received June 9, 2013.
- Revision received August 6, 2013.
- Accepted August 10, 2013.
- Copyright © 2013, American Association for Cancer Research.