Objective: Pancreatic cancer has remained one of the most devastating diseases over the past two decades, with minimal improvements in survival rates. Its highly immunosuppressive tumour microenvironment is driven by secreted proteins, such as cytokines and growth factors, which promote the differentiation of immunosuppressive cells and influence cellular proliferation and migration. This study investigates how the secretome from pancreatic cancer and pancreatic stellate cells affects the proliferation of myeloid-derived suppressor cells and its implications for cellular proliferation.

Patients and Methods: Conditioned media from pancreatic cancer cells and pancreatic stellate cells were used to treat peripheral blood mononuclear cells, evaluating their effects on myeloid-derived suppressor cells proliferation. Additionally, pancreatic stellate cells were treated with conditioned medium from pancreatic cancer cells to assess its impact on their proliferation. Conversely, conditioned medium from pancreatic stellate cells was used to treat pancreatic cancer cells to evaluate its effects on their growth.

Results: Conditioned media from both pancreatic cancer and pancreatic stellate cells significantly enhanced the proliferation of myeloid-derived suppressor cells, although the BrdU proliferation assay revealed differing outcomes. Conditioned media from primary pancreatic cancer cells notably increased the proliferation of pancreatic stellate cells more than that from metastatic cancer cells. Similarly, primary pancreatic cancer cells exhibited greater proliferation when exposed to conditioned media from pancreatic stellate cells compared to metastatic cells.

Conclusions: The bioactive secreted proteins from pancreatic cancer and pancreatic stellate cells effectively stimulate the proliferation of myeloid-derived suppressor cells without direct cell-to-cell interactions. Factors from primary tumour cells support cancer cell survival more than those from metastatic cells, indicating potential targets for immunotherapy in early-stage cancers.