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.
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Abbreviations
- LC:
-
Lung cancer
- NSCLC:
-
Non-small cell lung cancer
- ICIs:
-
Immune checkpoint inhibitors
- PD1:
-
Programmed cell death-1
- PDL1:
-
Programmed cell death-ligand 1
- FDA:
-
Food and Drug Administration
- AAbs:
-
Autoantibodies
- irAEs:
-
Immune-related adverse events
- IgG:
-
Immunoglobulin G
- IgM:
-
Immunoglobulin M
- AIH:
-
Type 1 autoimmune hepatitis
- RA:
-
Rheumatoid arthritis
- SLE:
-
Systemic lupus erythematosus
- NC:
-
Normal controls
- ELISA:
-
Enzyme-linked immunosorbent assay
- BSA:
-
Bovine serum albumin
- HRP:
-
Horseradish peroxidase
- TMB:
-
Tetramethyl benzidine
- H2O2 :
-
Hydrogen peroxide
- OD:
-
Optical density
- CV:
-
Coefficient of variation
- IIF:
-
Indirect immunofluorescence
- CI:
-
Confidence internal
- AUC:
-
Area under curve
- YI:
-
Youden’s index
- ROC:
-
Receiver operating characteristics
- ADC:
-
Lung adenocarcinoma
- SCC:
-
Lung squamous cell carcinoma
- LM:
-
Lymph node metastasis
- DM:
-
Distant metastasis
- OR:
-
Odds ratio
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Funding
This work was supported by the Leading Talents of Science and Technology Innovation in Henan Province (Grant Number 20420051008), the National Natural Science Foundation of China (Grant Number 8167291), the Key Project of Discipline Construction of Zhengzhou University (Grant Number XKZDQY202009).
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LPD supervised the study and approved the final version of the manuscript. JQL and ML performed experiments. JQL wrote the paper. LTJ and YTZ collected the data. XZ and TY interpreted the data. ZW and FFL collected the samples. JQL analyzed the data.
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Li, J., Liu, M., Zhang, X. et al. Plasma autoantibodies IgG and IgM to PD1/PDL1 as potential biomarkers and risk factors of lung cancer. J Cancer Res Clin Oncol 149, 4465–4475 (2023). https://doi.org/10.1007/s00432-022-04360-z
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DOI: https://doi.org/10.1007/s00432-022-04360-z