Peritoneal NK cells are responsive to IL-15 and percentages are correlated with outcome in advanced ovarian cancer patients

Abstract

The demonstration that ovarian carcinoma (OC) is an immunogenic disease,opens opportunities to explore immunotherapeutic interventions to improve clinicaloutcome. In this regard, NK cell based immunotherapy could be promising as it hasbeen demonstrated that OC cells are susceptible to killing by cytokine-stimulatedNK cells. Here, we evaluated whether percentage, phenotype, function and IL-15responsiveness of ascites-derived natural killer (NK) cells is related to progressionfree survival (PFS) and overall survival (OS) of advanced stage OC patients. Generally,a lower percentage of NK cells within the lymphocyte fraction was seen in OC ascites(mean 17.4 & 2.7%) versus benign peritoneal fluids (48.1 6.8% p 0.0001).Importantly, a higher CD56+ NK cell percentage in ascites was associated with abetter PFS (p = 0.01) and OS (p = 0.002) in OC patients. Furthermore, the functionalityof ascites-derived NK cells in terms of CD107a/IFN-activity was comparable to thatof healthy donor peripheral blood NK cells, and stimulation with monomeric IL-15 orIL-15 superagonist ALT-803 potently improved their reactivity towards tumor cells. Byshowing that a higher NK cell percentage is related to better outcome in OC patientsand NK cell functionality can be boosted by IL-15 receptor stimulation, a part of NKcell immunity in OC is further deciphered to exploit NK cell based immunotherapy.