HSP70-NK and Target Cell Interactions: Implication to the Anticancer Effects

Heat shock protein 70 (HSP70) and HSP70-based vaccine constructs are perspective tools for anticancer therapy. One of the established anticancer effects of HSP70 is activating natural killer (NK) cells. Moreover, HSP70-activated NK cells demonstrate effectiveness in preclinical glioblastoma and lung cancer models. It is thought that the expression of HSP70 on the surface of cancer cells stimulates the cytotoxic activity of NK cells. Regarding this, the spatial aspects of NK cells with cancer cells in the presence of HSP70 are essential but not properly investigated. Using confocal laser scanning microscopy, we have recently shown that exogenously added HSP70 is absorbed on the surface of dying NK cells, while live NK cells internalize the protein. In the present study, we visualized the spatial aspects of NK cell interactions with the target breast cancer cell line BT-20 in the presence of exogenous HSP70. We traced the uptake of HSP70 by BT-20 cells and investigated NK cell behavior and contacts with BT-20 cells in the presence of HSP70. The data obtained in the present study on the interaction of BT-20 cells, NK cells, and HSP70 revealed novel aspects of HSP70-mediated anticancer efficacy of NK cells.