Potential Efficacy of Anti-PD-1 or PD-L1 Antibody Treatments for Gynecologic Cancers.
Programmed cell death-1 (PD-1; CD279) is an immunosuppressive co-inhibitory molecule that belongs to the CD28 family of receptors on T-cells. It was discovered by Ishida et al in 1992. The most important peripheral regulatory pathway is the interaction between the PD-1 receptor, expressed on T-cells, and programmed cell death ligands-1 and 2 (PD-L1 and PD-L2)
on the cancer cell surface.
This immune checkpoint exists in a normal physiological state to protect against autoimmunity and inflammation. In a neoplastic state, dysfunction of these immune checkpoint proteins can lead to tumor tolerance and eventually allow tumors to ‘escape’ from the immune system. PD-1 blockage enhances the proliferation of transferred T-cells at the tumor site. In addition, the combination of adoptive T-cell transfer and anti-PD-1 antibody results in significant inhibition of tumor progression. These therapeutic effects of PD-1 blockage require the INF-γ signal. Targeting the molecules that regulate the immune response using the new drug nivolumab, an anti-PD-1 antibody has been the subject of much research and has yielded some promising and exciting results.
However, there have been few reports of anti-PD-1 or anti-PD-L1 treatments for gynecologic cancers. Hamanishi et al treated 20 patients with platinum-resistant ovarian cancer with an intravenous infusion of an anti-PD-1 antibody (nivolumab) every 2 weeks at 1 or 3 mg/kg.8
The best overall response was 15%, which included 2 patients who had a durable complete response (2CR; 1 partial response (PR)). There are few reports concerning the efficacy of anti-PD-L1/PD-1 immunotherapies for endometrial cancer.
Women Health Open J. 2017; 3(3): e21- e23. doi: 10.17140/WHOJ-3-e013
