Apoptosis induction in ovarian cancer cells

The immune system is in principle capable of detecting and eliminating tumor cells. However, a potent antitumor response usually does not occur. In contrast, virus infections lead to prompt immune activation and infected cells are immediately destroyed. Toll-like receptors (TLRs) recognizing nucleic acids are critical in the detection of cytopathic viruses and the subsequent triggering of an immune response. While the activity of endosomal nucleic acid receptors (TLR3, –7, –8, –9) is restricted mainly to immune cells, cytosolic nucleic acid receptors (RIG-I, MDA–5, DNA receptor) are ubiquitously expressed and may therefore serve as promising targets for cancer immunotherapy. We aimed to evaluate, if specific synthetic ligands of cytosolic receptors are able to stimulate tumor cells, to drive them into apoptosis, and thereby to increase their immunogenicity. Initially, we established cultures from cells in ascites diagnosed as ovarian adenocarcinoma. Using this in vitro model, we demonstrated that the engagement of cytosolic receptors is sufficient to induce apoptosis. In contrast, activation of endosomal receptors as well as TLR4, which recognizes bacterial wall components, showed no proapoptotic effect. Thus, our analysis opens the perspective of future therapeutic approaches with agents that are able to both directly destroy tumor cells and enhance the immune response against the tumor.

apoptosis - cytosolic nucleic acid receptors - innate immune system - ovarian cancer