Immune system plays an ambivalent role in cancer because is able to promote both suppression and progression of the tumor. Thus, immune cells can act against tumors recognizing specific tumor-associated antigens, but immunosuppressive factors in the microenvironment promote the modulation of immune cells towards a pro-tumorigenic phenotype. Accordingly, the tumor microenvironment (TME) is a key immunosuppressive space in which tumor progression is stimulated and also represents an obstacle for efficient tumor immunotherapy. A panoply of mechanisms are used by tumors to evade immune destruction including expansion and recruitment of immunosuppressive cells into their microenvironment (Schreiber et al., 2011). Among the most prominent subsets of tumor-induced immunosuppressive cells, myeloid-derived suppressor cells (MDSCs) are one of the most important. These cells form a heterogeneous group of immature monocytic and granulocytic cells, which are a rare group of myeloid cells in healthy hosts, but they accumulate progressively in blood, lymphoid organs, and within the TME as tumor burden increases. In fact, the increase of MDSCs in the TME seems to help tumor growth and correlates with poorer clinical outcomes. Likewise, low-circulating MDSCs were associated with better responses in patients with relapsed/refractory diffuse large B-cell lymphoma treated with R2-GDP (Palazón-Carrión et al., 2022). Thus, MDSCs are potential predictors for clinical progression and could be targets for immunotherapeutic strategies. Immunotherapy is used in several types of cancer and the number of eligible patients continues increasing; but it is important to understand how MDSCs impact on the different types of cancer, and their interplay with tumor cells in order to choose the appropriate immunotherapy.

In sarcomas, immunotherapy also offers new alternatives to treatment, because several studies have evidenced the role of the immune system in treating sarcomas. But due to a lack of pre-clinical models and the rarity of this tumor, the advances in treatment have been limited thus far. Identifying the role of immune cells and, in particular, MDSCs, could move the immunotherapy forward and may lead to important therapeutic opportunities in sarcomas. However, the role of MDSCs has not been fully studied and understood, which limits the development of immunotherapy in these tumors.

This chapter aims at providing a comprehensive overview of the role of MDSCs in sarcoma. Hence, MDSCs will be defined in order to understand both their role in sarcomas and their potential as a therapeutic target in this cancer.