Immune profiling and identification of prognostic immune-related risk factors in human ovarian cancer

ABSTRACTSuppression of immune reactivity by increased expression of co-inhibitory receptors has been discussed as a major reason as to why the immune system fails to control tumor development. Elucidating the co-inhibitory expression pattern of tumor-infiltrating lymphocytes in different cancer types will help to develop future treatment strategies. We characterized markers reflecting and affecting T-cell functionality by flow cytometry on lymphocytes isolated from blood, ascites and tumor from advanced ovarian cancer patients (n = 35). Significantly higher proportions of CD4+ and CD8+ T-cells expressed co-inhibitory receptors LAG-3, PD-1 and TIM-3 in tumor and ascites compared to blood. Co-expression was predominantly observed among intratumoral CD8+ T-cells and the most common combination was PD-1 and TIM-3. Analysis of 26 soluble factors revealed highest concentrations of IP-10 and MCP-1 in both ascites and tumor. Correlating these results with clinical outcome revealed the proportion of CD8+ T-cells w...