Stress-induced Feeder Cell-mediated Enhancement of NK Cell Proliferation

초록

Natural killer (NK) cells are immune cells phenotypically characterized as CD3-, CD16+ and CD56+, and are responsible for innate immunity within the body. Recently, NK cells have garnered attention as a promising candidate for allogeneic therapy. Unlike T cells utilized in traditional cell therapies, NK cells do not necessitate being derived from the patient's cells to serve as an effective therapeutic agent [1]. However, the limited half-life of NK cells is a major limitation of their therapeutic application. Various attempts have been made to introduce feeder cells to overcome this drawback, but safer methods are needed. In our study, we confirmed that the expression of 4-1BBL in Colo-205 cells increased when exposed to extracellular stresses, such as hypoxia and cytochalasin D. The upregulation of 4-1BBL expression facilitates binding between 4-1BBL molecules on the surface of feeder cells and 4-1BB receptors on the surface of NK cells. Subsequently, the 4-1BB/4-1BBL binding promotes the proliferation of NK cells [2]. Furthermore, it is reported that NK cells with higher CD56 expression exhibit enhanced proliferation [3]. To validate this, we investigated the expression of CD56 in NK cells post co-culture, examining both the protein and gene levels. Our findings revealed a significant upregulation of CD56 expression in both protein and gene analyses. Colo-205 cells were exposed to extracellular stresses such as hypoxia and cytochalasin D, effectively converting them into feeder cells. Subsequent co-culture with NK cells significantly enhanced NK cell proliferation.