Abstract:
Background
Immunosuppressive microenvironment of pancreatic cancer pancreatic ductal adenocarcinoma cell (PDAC) and pancreatic stellate cell (PSC) comprise myeloid derived suppressor cells (MDSC) which greatly contribute in impaired antitumour response, as well as progression of tumour. It was previously (unpublished) reported that physical contact of PDAC and PSC with peripheral blood mononuclear cells (PBMC) can convert PBMC into MDSC, causing suppression of T cells proliferation and activity. Little is known on the role of PDAC or combined with PSC in MDSC differentiation. In order to better mimic the tumour microenvironment, the effects of PDAC and PSC on PBMC was investigated via incubation with conditioned media prepared from supernatant of PDAC and PSC co-culture.
Methods
PBMCs were incubated with conditioned media prepared from supernatant of PDAC and PSC co-culture. The differentiation of PBMC to MDSC and their subtypes, polymorphonuclear-MDSC (p-MDSC) and mononuclear-MDSC (m-MDSC) were analysed using flow cytometer.
Results
This study had shown that secreted molecules from PDAC and PSC alone can induce the differentiation of MDSC and thus increase the percentage of MDSC in the total cell population. Secreted molecules from PDAC and PSC combination can also increase the ratio of p-MDSC to m-MDSC.
Conclusion
The secreted molecules in conditioned media alone is able to increase the ratio of p-MDSC : m-MDSC, even though there is no physical contact between PDAC, PSC and PBMC.
