Immune evasion is a recently defined hallmark of cancer, and immunotherapeutic approaches that stimulate an immune response to tumours are gaining recognition. However tumours may evade the immune response and resist immune‐targeted treatment by promoting an immune‐suppressive environment and stimulating the differentiation or recruitment of immunosuppressive cells. Myeloid‐derived suppressor cells (MDSC) have been identified in a range of cancers and are often associated with tumour progression and poor patient outcomes. Pancreatic cancer in particular supports MDSC differentiation via the secretion of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), and MDSC are believed to contribute to the profoundly immune‐suppressive microenvironment present in pancreatic tumours. MDSC‐targeted therapies that deplete or inhibit this cell population have been proposed as a way to shift the balance in favour of a tumour‐clearing immune response. In this study, we have modelled MDSC differentiation and function in vitro and this has provided us with the opportunity to test a range of potential MDSC‐targeted therapies to identify candidates for further investigation. Using in vitro modelling we show here that the combination of GM‐CSF‐signalling blockade and gemcitabine suppresses both the MDSC phenotype and the inhibition of T‐cell function by MDSC.