The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion

Abstract

Suppression of antitumor immune responses is one of the main mechanisms by which tumor cells escape from destruction by the immune system. Myeloid-derived suppressor cells (MDSCs) represent the main immunosuppressive cells present in the tumor microenvironment (TME) that sustain cancer progression. MDSCs are a heterogeneous group of immature myeloid cells with a potent activity against T-cell. Studies in mice have demonstrated that MDSCs accumulate in several types of cancer where they promote invasion, angiogenesis, and metastasis formation and inhibit antitumor immunity. In addition, different clinical studies have shown that MDSCs levels in the peripheral blood of cancer patients correlates with tumor burden, stage and with poor prognosis in multiple malignancies. Thus, MDSCs are the major obstacle to many cancer immunotherapies and their targeting may be a beneficial strategy for improvement the efficiency of immunotherapeutic interventions. However, the great heterogeneity of these cells makes their identification in human cancer very challenging. Since both the phenotype and mechanisms of action of MDSCs appear to be tumor-dependent, it is important to accurately characterized the precise MDSC subsets that have clinical relevance in each tumor environment to more efficiently target them. In this review we summarize the phenotype and the suppressive mechanisms of MDSCs populations expanded within different tumor contexts. Further, we discuss about their clinical relevance for cancer diagnosis and therapy.

Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities

“…MDSCs play a critical role in regulating anticancer immunity in the TME as well as resistance to PD-1/PD-L1 antibodies. MDSCs are a diverse population of myeloid cells existing in various states of differentiation that display potent immune suppressive functions (81,82). MDSCs also potentiate angiogenesis via different mechanisms (83).…”

The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment

“…This discrepancy in the patients’ responses toward ICI is partly explained by immune-suppressive effects, which are elicited by the diverse character of the immune milieu that exists within the TME, since patients with immunologically anergic tumors are likely to be non-responsive to ICI therapy [ 250 ]. Most notably, recent reports suggest that MDSC-mediated immunosuppression substantially contributes to tumor immune evasion [ 28 , 251 ].…”

Phenotypes, Functions, and Clinical Relevance of Regulatory B Cells in Cancer

“…MDSCs are a group of immature cells that are potent in immune suppressors in cancer (83)(84)(85). The expansion of MDSCs has often been recognized as an indicator of tumor burden and metastasis (86,87).…”