Cellular Biomarker for the Responding of Anti-PD-1 Therapy in Non-Small Cell Lung Cancer Patients

Abstract

Immune checkpoint inhibitors which have been actively used and studied in recent years opened a new era in cancer immunotherapy. The strategy that targeting Programmed cell death protein1 (PD-1) and its ligand Programmed cell death protein ligand1 (PD-L1) to block their function showed us surprising results in many clinical and pre-clinical studies. Nivolumab and Pembrolizumab which are fully humanized anti-PD-1 therapeutic antibody have been used for cancer immunotherapy in many types of cancers. Because of their powerful anti-tumor effect, long duration time and acceptable side effects, they could achieve big success in pharmaceutical market. However, high cost and low drug response rate limit their practical and common usage of the drugs. Despite of many trials to find out predictive biomarkers, there are no reliable markers found so far. For the biomarker of anti-PD-1 therapy, tumor expression status of PD-L1 by immunohistochemistry (IHC) staining has been used, but it has many problems concerning the accuracy of prediction and unstandardized protocols. Here we found cellular biomarker for anti-PD-1 therapy which can powerfully predict the drug response with better accuracy and simplified way compared to the conventional IHC-based tumor PD-L1 expression marker. We checked lymphocytes as immune active cells and myeloid-derived suppressor cell (MDSC) for the suppressive immune cells based on our hypothesis that the drug response for the immune checkpoint blockade depends on the systemic immune status of the individual patient. Peripheral blood regulatory T cell (Treg)/ Lectin-type oxidized LDL receptor-1 (Lox-1)+ PMN-MDSC ratio after the first infusion of anti-PD-1 drug significantly higher in responder group. Its cut-off value gives us the outstanding prediction accuracy for the patient prognosis, so we can expect it as a strong biomarker for anti-PD-1 therapy.