1945P Distribution of anti-PD1/PDL1 autoantibodies in multiple cancer types and potential biomarker role for anti-PD1 therapy

Abstract

Antibodies targeting programmed cell death protein 1(PD1) and its ligand (PDL1) have revolutionized cancer therapy. However, little is known about the preexisted anti-PD1/PDL1 antoantibodies (AAbs) IgG and subclass distribution in cancer patients, nor is their potential role for anti-PD1 therapy. We used enzyme linked immune sorbent assay (ELISA) to examine serological anti-PD1/PDL1 IgG AAb and subclasses (IgG1-4) in 189 cancer patients without anti-PD1 therapy, covering 10 types of cancers (lung, breast, esophageal, colorectal, liver, prostatic, cervical, ovarian, gastric cancers and lymphoma). We further tested the anti-PD1/PDL1 AAb IgG, IgG1 and IgG2 in 16 non-small cell lung cancer (NSCLC) baseline plasma samples receiving anti-PD1 therapy, the association of AAb IgG subclasses with clinical parameters and overall survival were analyzed. Anti-PD1 AAb IgG and anti-PDL1 AAb IgG were globally detected in 10 types of cancer patients. Anti-PD1 AAb IgG was highest in breast cancer and lowest in colorectal cancer, while anti-PDL1 AAb IgG was highest in liver cancer and lowest in cervical carcinoma. Of the IgG subclasses, IgG1 and IgG2 were revealed to be the major subtypes for both anti-PD1 and anti-PDL1 AAbs in 10 cancer types. In 16 NSCLC patients receiving anti-PD1 therapy, the anti-PD1 IgG2 and anti-PDL1 IgG2 were significantly associated with white blood cell count(r=0.554, p=0.026; r=0.586, p=0.017), absolute neutrophil count(r=0.577, p=0.019; r=0.626, p=0.009) and absolute monocyte count (r=0.683, p=0.004; r=0.729, p=0.001). Higher anti-PD1 IgG2 was revealed to associate with improved anti-PD1 therapeutic survival, though no statistical significance were reached which may due to limited samples. This study reports for the first time the distribution of preexisted anti-PD1/PDL1 AAb and their subclasses in a wide range of cancer types. Moreover, the PD1 IgG2 were identified to associate with clinical parameters and may serve as potential biomarkers to predict anti-PD1 therapeutic survival in NSCLC and guide anti-PD1 treatment for cancer patients.