Provided are compositions and methods of use thereof that modulate C/EBP homologous stress-related protein (Chop) activity in Myeloid-derived Suppressor Cells (MDSCs). Chop is a key point in the response of MDSCs to tumor-generated stress factors. In turn, the MDSCs release cytokines and other factors that function as immune suppressors, thereby allowing the tumors to thrive and expand. By inhibiting the level of Chop activity, the immunosuppressive function of MDSCs is disrupted. It has also been unexpectedly found that there is a concomitant increase in the ability of MDSCs to act as antigen-presenting and cytokine producing cells so as to act in increasing the efficacy of anti-tumor immune-based therapies.