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

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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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Authors and Affiliations

  1. Henan Institute of Medical and Pharmaceutical Sciences & School of Basic Medical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, 450052, Henan, China

    Jiaqi Li, Man Liu, Xue Zhang, Yutong Zhao & Liping Dai

  2. BGI College, Zhengzhou University, Zhengzhou, 450052, Henan, China

    Longtao Ji, Ting Yang, Zhi Wang, Feifei Liang & Liping Dai

  3. Henan Key Laboratory of Tumor Epidemiology & State Key Laboratory of Esophageal Cancer Prevention, Zhengzhou University, Zhengzhou, 450052, Henan, China

    Jiaqi Li, Man Liu, Xue Zhang, Yutong Zhao & Liping Dai

  4. Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, 450052, Henan, China

    Jiaqi Li, Man Liu, Xue Zhang, Longtao Ji, Ting Yang, Yutong Zhao, Zhi Wang, Feifei Liang & Liping Dai

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  1. Jiaqi Li
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  2. Man Liu
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  9. Liping Dai
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Contributions

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.

Corresponding author

Correspondence to Liping Dai.

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Approval of the research protocol by the First Affiliated Hospital of Zhengzhou University.

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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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