Programmed Death-1 (PD-1) and PD-1 Ligand (PD-L1) are immune checkpoint proteins that are crucial for self-tolerance.
Induction of the PD1/PD-L1 pathway represents an adaptive immune resistance mechanism exerted by tumor cells in response to endogenous antitumor activity.
FDA approved Immuno-oncology agent, the PD-1 inhibitors Pembrolizumab , for the treatment of previously treated advanced Non-Small cell Lung Cancer (NSCLC), Both work by blocking PD-1 on the surface of immune cells, disrupting its interaction with PD-L1 on cancer cells. This lifts a natural brake on the immune system (i.e., PD-1), allowing it to kill cancer cells.
PDL-1 expression is important to identify patients most likely to benefit from therapy.
Patients with metastatic NSCLC whose tumors have high PD-L1 expression [(Tumor Proportion Score (TPS) =50%)] with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC.
Patients with metastatic NSCLC whose tumors express PD-L1 (TPS =1%) with disease progression on or after platinum-containing chemotherapy.
Clinical utility
To assess PD-L1 expression in Non-squamous NSCLC tissue specimens.
Aids in identifying patients who will benefit from Pembrolizumab.
When to test:
Test patients for PDL-1 expression at time of diagnosis, concurrent with differentiation of histologic subtypes.
In patients who were not tested at diagnosis, testing prior to second line or greater treatment can also inform treatment decisions.