Use Of Myeloid-Derived Suppressor Cells As A Targeted And Promising Delivery System For Tumor Immunotherapy

The highly important roles of immune system in cancer development has made immune cells andtheir related factors as attractive research tools in cancer immunotherapy. One of these cell typesincludes myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloidprogenitor cells, i.e., immature granulocytes, macrophages, and dendritic cells (DCs). Two majortypes of MDSCs are: CD11b+Gr1high (CD11b+Ly6G+Ly6Clow) with a granulocytic phenotype(gMDSC), and CD11b+Gr1low (CD11b+Ly6G-Ly6Chigh) with a monocytic phenotype (mMDSC). Incancer patients, these immature cells, in response to some tumor related cytokines or factors suchas GM-CSF or S100, migrate from the bone marrow to primary or metastatic tumors. These tumorsblock their differentiation to mature cells and instigate them to produce some immunosuppressivecytokines such as IL-6, IL-10, and TGF-β, and some factors such as arginase 1, reactive oxygenspecies (ROS) and inducible nitric oxide synthetase, that modulate cancer cell killing responses of Tcells and natural killer cells in the tumor microenvironment (TME). In tumor-bearing mice, ROSimpair DC maturation while sustaining the accumulation of myeloid-derived cells with an immaturephenotype, i.e. MDSCs. Due to specifically homing of MDSCs in tumors, in recent studies, MDSCshave been used for specific delivery of curative agents to TME in two approaches: first, as vehiclesfor delivery of immune cells activator agents, such as bacteria, to tumors; afterwards, this infectedtumor cells will become a target for the activated immune cells. In second approach, MDSCs havebeen used as delivery systems for tumor cytotoxic agents to TME; in case of engineered tumorkilling bacteria, injection of bacteria-infected MDSCs into the tail vein of tumor-bearing mice,resulted in selectively delivery of bacteria to metastatic sites, where it could spread from One cellto another without being eliminated by the immune system; however, it was very poorly deliveredto normal tissues such as spleen. These observations indicate high capacity of MDSCs to be targetedto various histological types of cancers and highlight the great potential of immune cells thatnaturally home to the TME for selective delivery of anticancer agents.