Nanoengineered drug delivery in cancer immunotherapy for overcoming immunosuppressive tumor microenvironment

Almost like a living being in and of itself, tumors actively interact with and modify their environment to escape immune responses. Owing to the pre-formation of cancer-favorable microenvironment prior to anti-cancer treatment, the numerous attempts that followed propose limited efficacy in oncology. Immunogenicity by activation of immune cells within the tumor microenvironment or recruitment of immune cells from nearby lymph nodes is quickly offset as the immunosuppressive environment, rapidly converting immunogenic cells into immune suppressive cells, overriding the immune system. Tumor cells, as well as regulatory cells, namely M2 macrophages, T_reg cells, and MDSCs, derived by the immunosuppressive environment, also cloak from potential anti-tumoral factors by directly or indirectly secreting cytokines, such as IL-10 and TGF-β, related to immune regulation. Enzymes and other metabolic or angiogenetic constituents — VEGF, IDO1, and iNOS — are also employed directed for anti-cancer immune cell malfunctioning. Therefore, the conversion of “cold” immunosuppressive environment into “hot” immune responsive environment is of paramount importance, bestowing the advances in the field of cancer immunotherapy the opportunity to wholly fulfill its intended purpose. This paper reviews the mechanisms by which tumors wield to exercise immune suppression and the nanoengineered delivery strategies being developed to overcome this suppression. Graphical Abstract: [Figure not available: see fulltext.]