Modulation of PD-1/PD-L1 axis in myeloid-derived suppressor cells by anti-cancer treatments

• Only a subset of patients responds to immunotherapy with PD-1/PD-L1 blockade (ICB). • PD-L1 can be present on both tumor cells and immune cells in the microenvironment. • Cancer therapies can differently shape MDSCs recruitment, function and PD-L1 levels. • Similar effects can be induced by metabolism and lifestyle interventions. • Combination with ICB could be synergic or useless for given therapy and tumor type. Immuno checkpoint blockade (ICB) targeting the PD-1/PD-L1 axis is the main breakthrough for the treatment of several cancers. Nevertheless, not all patients benefit from this treatment and clinical response not always correlates with PD-L1 expression by tumor cells. The tumor microenvironment, including myeloid derived suppressor cells (MDSCs), can influence therapeutic resistance to ICB. MDSCs also express PD-L1, which contributes to their suppressive activity. Moreover, anticancer therapies including chemotherapy, radiotherapy, hormone- and targeted- therapies can modulate MDSCs recruitment, activity and PD-L1 expression. Such effects can be induced also by innovative anticancer treatments targeting metabolism and lifestyle. The outcome on cancer progression can be either positive or negative, depending on tumor type, treatment schedule and possible combination with ICB. Further studies are needed to better understand the effects of cancer therapies on the PD-1/PD-L1 axis, to identify patients that could benefit from combinatorial regimens including ICB or that rather should avoid it.