Potential Efficacy of Anti-PD-1 or PD-L1 Antibody Treatments for Gynecologic Cancers
Keywords:
immunosuppressive, neoplastic stateAbstract
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 1992.1
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.2
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.3
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