Designing new nanoliposomal formulations and evaluating their effects on myeloid‐derived suppressor cells and regulatory T cells in a colon cancer model aiming to develop an efficient delivery system for cancer treatment; an in vitro and in vivo study

Abstract

Regulfatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) are common immunosuppressive cells in the tumor microenvironment. These cells, through various mechanisms, inhibit antitumor immune responses and impede effective therapies. Therefore, designing an efficient protocol for inducing immune surveillance in tumors is highly recommended. Recently, nanoliposomes have provided broad-spectrum and state-of-the-art vehicles to deliver antigens or immune system compartments in immunotherapies. It has been shown that different lipids in the structure of liposomes and various liposomal formulations can affect immune responses in the tumor microenvironment. This study was aimed to evaluate the effects of four different liposomal formulations on MDSCs and Tregs in C26 tumor-bearing mice. To this end, after preparing liposomes, they were injected into tumor-inoculated mice and analyzed MDSC and Treg population and functions in spleen and tumor tissues. Results showed that 1,2-dioleoyl-3-trimethylammonium propane (DOTAP)-containing liposomes reduced MDSC population and activity in the spleen, but not tumor, compared with other groups significantly (p<0.05 and p < 0.01, respectively). Moreover, DOTAP-containing liposomes reduced the expression of S100A8 and arginase-1 genes in splenic MDSCs (p<0.05). In conclusion, we provided evidence that DOTAP-containing liposomes contributed to stimulating immune responses and provided a situation to inhibit immunosuppression in the tumor microenvironment.