Abstract:
MDSC, or myeloid-derived suppressor cells, have recently emerged as the ‘mastermind’ of the PDAC tumour microenvironment as it provides cancer cells with an advantage in manipulating immune system control, allowing tumour expansion, invasion, and progression resistance. Even though PDAC and adjacent stromal PSC have been shown to influence MDSC differentiation, little is known about their impact on MDSC viability and proliferation, especially in metastatic conditions. PDAC aggression and resistance to current therapy necessitate a thorough understanding of MDSC behaviour in the context of the tumour microenvironment, as findings from this can provide critical insight for improving treatment efficacy and be a potentially game-changing advancement in pancreatic cancer management. Keeping this in mind, the purpose of this study is to see how conditioned media derived from human metastatic PDAC, human immortalised PSC, and human metastatic PDAC/human immortalised PSC co-culture affect the viability and proliferation of MDSC. To do so, we cultured MDSC isolated from human peripheral mononuclear cells (PBMCs) with human metastatic PDAC, human immortalised PSC, and human metastatic PDAC/human immortalised PSC co-culture conditioned media and validated the investigated parameter using CellTiter-Glo® and BrdU assays. This study discovered that conditioned media (CM) from human metastatic PDAC cells increased the viability and proliferation of MDSC cultures significantly more than human immortalised PSC or human metastatic PDAC/PSC co-culture. This implies that direct tumour interaction between metastatic PDAC, PSC, and MDSC may not be necessary for MDSC proliferation. In summary, this study sheds light on the production and release of
molecules that target the expansion of MDSC populations, as well as how conditioned media concentrations can influence MDSC regulation during the emergence of metastatic PDAC and PSC in humans, potentially aiding in the reduction of pancreatic cancer and its mortality rate.
