IL15 Infusion of Cancer Patients Expands the Subpopulation of Cytotoxic CD56bright NK Cells and Increases NK-Cell Cytokine Release Capabilities

The cytokine IL15 is required for survival and activation of natural killer (NK) cells as well as expansion of NK-cell populations. Here, we compare the effects of continuous IL15 infusions on NK-cell subpopulations in cancer patients. Infusions affected the CD56(bright) NK-cell subpopulation in that the expansion rates exceeded those of CD56(dim) NK-cell populations with a 350-fold increase in their total cell numbers compared with 20-fold expansion for the CD56(dim) subset. CD56(bright) NK cells responded with increased cytokine release to various stimuli, as expected given their immunoregulatory functions. Moreover, CD56(bright) NK cells gained the ability to kill various target cells at levels that are typical for CD56(dim) NK cells. Some increased cytotoxic activities were also observed for CD56(dim) NK cells. IL15 infusions induced expression changes on the surface of both NK-cell subsets, resulting in a previously undescribed and similar phenotype. These data suggest that IL15 infusions expand and arm CD56(bright) NK cells that alone or in combination with tumortargeting antibodies may be useful in the treatment of cancer. (C) 2017 AACR.