Influence of the molecular subtype of epithelial ovarian cancer on MDSC induction

Myeloid derived suppressor cells (MDSC) represent a heterogeneous group of cells which expansion was first associate to the presence of cancer. MDSC are functionally defined as suppressive of the T cell activation, which as a consequence positively correlate with the cancer progression. Improvements in the oncology filed have shed light on a better characterization of certain type of cancer. However, due to the heterogeneity and multifaced complexity of the disease, these findings cannot be applied universally. Among all the cancers, epithelial ovarian cancer (EOC), is the deadliest gynecological malignancy. In this work, ovarian cancer (OC) patients show that MDSC levels in the peripheral blood are significantly upregulated compared to the controls. Furthermore, the t-SNE dimensionality reduction analysis allows to highlight the presence of differences in the lymphocyte compartment of the circulatory system, suggesting alterations which should be disclosed. Tan et al. (2013) reported that EOC, and relative cell lines, can be classified in five distinct molecular subtypes: Epi-A and Epi-B (epithelial signature), Stem-A and Stem-B (stem cell signature), and Mes (mesenchymal signature). The results obtained in this work focus on the different capacity of ovarian tumour cell lines, each belonging to one molecular subtype (UWB1.289, CAOV-3, OVCAR-3, OV-90, and SKOV-3, respectively) to induce efficiently the MDSCs. In particular, the Mes molecular subtype associated to poorer outcome shows to have the highest capacity to induce the MDSCs. On the contrary, the other molecular subtype, associated to a better prognosis, shows little or none MDSC induction. Still, hurdles in isolating these tumour-induced MDSC are present, either in obtaining a pure population, or a sufficient cell number. This negatively impact on confirming the suppressive effect of the MDSC on T cell. OC patient not only shows high level of MDSC in peripheral blood. Indeed, the patient-derived tumour samples reveal the presence of infiltrating MDSC, underlying the involvement in EOC. Therefore, it is of paramount importance to establish stable patient-derived tumour cell lines to test the ability to induce the MDSC. The association between EOC molecular subtype, or the histological subtype, with the induction of MDSC may reveal and replicate what it was observed in the in vitro model system.