PP4 inhibition sensitizes ovarian cancer to NK cell-mediated cytotoxicity via STAT1 activation and inflammatory signaling

Cancerous tumors grow and prosper in an inflammatory environment at the intersection of many signaling pathways in the immune system. Since tumors exist in such a complex environment, researchers have been interested in how targeting components and molecules in these signaling pathways could enable targeted therapy for cancer patients. The main challenge in such studies is that primary tumor samples are exceedingly difficult to study, particularly since each sample is comprised of rare cell populations that are difficult to isolate and characterize in a laboratory setting.  

Dr. Marion Curtis and her team Mayo Clinic recently employed an in vitro co-culture system to show that inhibiting a protein called protein phosphatase 4 (PP4), enhanced the anti-tumor functions of immune cells. This study used in vitro co-culture assays to show that inhibition or deficiency of PP4 results in increased sensitivity of Ovarian Cancer (OC) cells to carboplatin, a chemotherapeutic. These findings were then validated in vivo, with the group showing that knockdown of PP4C in a mouse model of OC resulted in decreased tumor growth and enhanced immune cell infiltration of the tumors in the mice. The co-culture assays were employed with the help of the Curiox Biosystems Laminar Wash Technology, which employs a gentle, centrifuge-less gravity-fed washing system that increases resolution, reproducibility, and cell viability, which is crucial to studies such as this that nominate potential clinical targets.  

Download this article to learn more about:  

• A role for PP4 in inflammatory signaling and immune cell infiltration in the context of ovarian cancer.  
• How inhibition of PP4 in vitro and in vivo could be of therapeutic benefit in ovarian cancer treatment.  
• Laminar Wash technology and how it enables co-culture assays to assess the potency of potential anti-tumor therapies.