Immunotherapy of targeting MDSCs in tumor microenvironment

Abstract

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous cells which are abnormally accumulated during the differentiation of myeloid cells. Immunosuppression is the main functional feature of MDSCs, which inhibit T cell activity in the tumor microenvironment (TME) and promote tumoral immune escape. The main principle for immunotherapy is to modulate, restore, and remodel the plasticity and potential of immune system to have an effective anti-tumor response. In the TME, MDSCs are major obstacles to cancer immunotherapy through reducing the anti-tumor efficacy and making tumor cells more resistant to immunotherapy. Therefore, targeting MDSCs treatment becomes the priority of relevant studies and provides new immunotherapeutic strategy for cancer treatment. In this review, we mainly discuss the functions and mechanisms of MDSCs as well as their functional changes in the TME. Further, we review therapeutic effects of immunotherapy against MDSCs and potential breakthroughs regarding immunotherapy targeting MDSCs and immune checkpoint blockade (ICB) immunotherapy.

Inflammation Control and Tumor Growth Inhibition of Ovarian Cancer by Targeting Adhesion Molecules of E-Selectin

“…MDSCs in mice have two distinct subtypes: CD11bLy-6GLy-6C ++high and CD11bLy-6GLy-6C ++low [ 46 ]; we detected both subtypes using flow cytometry and found an apparent reduction in the ESBP-BSANPs-PTX-treated group, showing a lower drug resistance and better drug effect in vivo. MDSCs are a population of immature myeloid cells that accumulate in patients with cancer [ 32 ] and have immunosuppressive properties [ 47 ]. MDSCs have been shown to play pleiotropic roles in cancer progression by promoting tumor cell proliferation, metastatic growth and drug resistance through immunosuppression and inflammation [ 48 ].…”

The rising roles of exosomes in the tumor microenvironment reprogramming and cancer immunotherapy

“…94 They promote tumor cells to become resistant to immunotherapy by inhibiting the antitumor activity, which is a major disturbance to cancer immunotherapy. 95 Targeted inhibition of M-MDSCs development significantly improve the efficacy of ICI therapy and prolong the survival time of tumor-bearing mice. 96 The communication between MDSCs and tumor cells is the driving force for the deterioration of various tumors.…”

Advanced Generation Therapeutics: Biomimetic Nanodelivery System for Tumor Immunotherapy

“…In addition, both regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) are involved in immunosuppression and tumor metastasis. Tregs inhibit T cell activity by releasing TGF-β and IL-10, while MDSCs restrict immune functions by secreting immunosuppressants as nitric oxide, arginase and reactive oxygen species. Moreover, TAMs are critical components of iTME and play a non-negligible role in promoting tumor inflammation and progression .…”