Targeted regulation of tumor microenvironment through the inhibition of MDSCs by curcumin loaded self-assembled nano-filaments

Abstract

One of the most important reasons underlying the resistance of tumors is the immune suppression induced by cancer cells. Myeloid-derived suppressor cells (MDSCs), which exerts pivotal functions in immunosuppression, is a key participator in tumor microenvironment and a novel target for cancer therapy. Here curcumin (Cur) was employed as a specific MDSCs repressor to inhibit the number and function of MDSCs. Moreover, a novel self-assembled nano-filament system was generated through the conjugation of Cur and a self-assembled peptide. In vivo study demonstrated the powerful antitumor effect of curcumin-loaded nano-filaments (Nano-Cur) with delayed tumor growth and longer survival. The immune status of tumor microenvironment (TME) was well improved by Nano-Cur treatment with increased T cell proliferation and activation as well as enhanced production of inflammatory mediators such as GM-CSF and IL-6, which revealed that Nano-Cur contributed to relieve the tumor burden by regulating and improving the TME. Furthermore, flow cytometry analysis implied the lower MDSCs levels under Nano-Cur treatment, which indicated that the anticancer effect of Nano-Cur may be associated with the inhibition of recruitment and accumulation of MDSCs in the TME. Therefore, Nano-Cur may be a novel therapeutic approach for lung cancer, and extensive studies of mechanisms are required to better understand how TME affects tumor progression and provide new insights into anticancer therapeutics.