Plasma autoantibodies IgG and IgM to PD1/PDL1 as potential biomarkers and risk factors of lung cancer

Abstract

Antibodies targeting programmed cell death-1 (PD1) and its ligand (PDL1) have transformed current cancer therapy while little is known about the expression of anti-PD1/PDL1 autoantibodies between lung cancer (LC) patients and normal controls (NC). The expression level of anti-PD1/PDL1 IgG and IgM was detected in plasma of 325 LC and 324 NC by indirect enzyme-linked immune sorbent assay (ELISA). Western blot and indirect immunofluorescence (IIF) were used to verify the ELISA results. The association analysis was used to evaluate the odds ratio (OR) of LC. The expression of anti-PD1/PDL1 IgG in LC samples was significantly higher than NC (P < 0.001 and P < 0.05, respectively). The positive rate of anti-PD1/PDL1 IgG in LC was significantly higher than NC and significant difference was also shown in LC samples of different clinical characteristics, such as clinical stage, nodules diameter, lymph node metastasis and distant metastasis (P < 0.001). Moreover, PD1/PDL1 expression in tissues showed no significant relation with that in plasma (P > 0.05). Anti-PD1/PDL1 IgG were the risk factors related to LC (OR (95% CI): 22.433 (5.426-92.745) and 5.051 (1.316-19.386)), while anti-PD1/PDL1 IgM were the risk factors for LC with ≤ 60 years (OR (95% CI): 6.122 (1.365-27.455) and 7.664 (1.715-34.251)) and anti-PD1 IgM was also the risk factor for male LC cases(OR (95% CI): 6.948 (1.076-44.868)). Plasma anti-PD1/PDL1 IgG and IgM might serve as potential biomarkers and risk predictors for LC.

Keywords: Anti-PD1/PDL1; Autoantibodies; Biomarker; LC; Risk factors.