Targeting the IL-6R/STAT3/PD-L1 axis: lobaric acid and Tocilizumab as a promising combination immunotherapy in ovarian cancer
Ovarian cancer is the most deadly gynecological malignancy, largely due to difficulties in early detection, therapeutic resistance and toxicity. The aim of this study was to evaluate the potential therapeutic effects of the small-molecule drug candidate lobaric acid (LA) as monotherapy and in combination with tocilizumab (TCZ) and atezolizumab (ATE) in ovarian cancer. In this study, the anti-proliferative and immunotherapeutic effects of LA, TCZ, and ATE in different ovarian cancer cell lines were determined. In addition, the intracellular signalling effects of LA and its combination with TCZ were extensively investigated by silencing the STAT3 pathway and the results were confirmed. This study demonstrated for the first time that the combination of LA and TCZ exerts a significant immunotherapeutic effect on ovarian cancer cells. LA treatment, either as monotherapy or in combination with TCZ, was found to have therapeutic potential for ovarian cancer without cytotoxic effects on healthy cells. These findings emphasise that LA is a promising candidate for the treatment of ovarian cancer and indicate its potential for inclusion in advanced treatment protocols.