Prognosis of ovarian cancer is associated with effector memory CD8(+) T cell accumulation in ascites, CXCL9 levels and activation-triggered signal transduction in T cells

The accumulation of intratumoral CD8(+) T cells is associated with the survival of high grade serous ovarian carcinoma patients, but it is unclear which CD8(+) T cell subsets contribute to this effect and how they are affected by the peritoneal tumor microenvironment. Here, we provide evidence for a functional link between long relapse-free survival, accumulation of CD8(+) effector memory T (T-EM) cells in peritoneal effusion (ascites), and the level of the CD8(+) T-EM attracting chemokine CXCL9, produced by macrophages as a major source. We also propose a novel mechanism by which the tumor microenvironment could contribute to T cell dysfunction and shorter survival, i.e., diminished expression levels of essential signaling proteins, including STAT5B, PLC gamma 1 and NFATc2. CD8(+) T-EM cells in ascites, CXCL9 levels and the expression of crucial signal transduction proteins may therefore be important biomarkers to gauge the efficiency of immune therapies and potentially represent therapeutic targets.