Figure 2.
Association of CXCL9 levels in ovarian cancer ascites with relapse-free survival (RFS). (A) Expression of the genes encoding CXCR3 and its ligands CXCL9, CXCL10 and CXCL11 in tumor cells (TU) depicted in red, tumor-associated macrophages (TAM) depicted in blue and tumor-associated T cells (TAT) depicted in green from ovarian cancer ascites (TPM values determined by RNA-Seq). (TU, n = 23; TAM, n = 28; TAT, n = 6). MSLN, CD163 and LCK served as cell-type-specific markers for TU, TAM and TAT, respectively. The highest value illustrated the highest expression level in each cell type. (B) Correlation of TAM numbers in ascites (CD14+ cells/ml) with the level of different soluble mediators in ascites determined by ELISA (Spearman rho; n = 17 patients). (C) Kaplan-Meier analysis of CXCL9 ascites levels as in panel A. Samples were dichotomized at the lower tercile (q = 0.3) as indicated. p: logrank p-value; HR: hazard ratio; rfs: RFS for high versus low levels; inf: infinite (> 56 months). (D) Association of the expression of CXCL and CXCR3 genes in tumor tissue with the overall survival (OS) of ovarian cancer patients. Data were retrieved from the PRECOG database (https://precog.stanford.edu). z-score <2 (blue): significant association with OS; z-score >2 (red): inverse association with OS; (E) Model depicting regulation of TEM migration into the ovarian cancer environment by TAM and association of TEM accumulation in ascites with prolonged RFS. TAM produce chemokines CXCL9, CXCL10 and CXCL11, which attract CXCR3 expressing TEM cells from the periphery, possible in concert with other mediators (dashed arrow). The TEM cells migrating into the TME contribute to tumor eradication and a longer survival.