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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 7/2022

24-11-2021 | Lymphoma | Original Article

Anti-PD1/PDL1 IgG subclass distribution in ten cancer types and anti-PD1 IgG4 as biomarker for the long time survival in NSCLC with anti-PD1 therapy

Authors: Qiaoyun Tan, Liyuan Dai, Yanrong Wang, Shuxia Liu, Te Liang, Rongrong Luo, Shasha Wang, Ning Lou, Haizhu Chen, Yu Zhou, Qiaofeng Zhong, Jianliang Yang, Puyuan Xing, Xingsheng Hu, Yutao Liu, Shengyu Zhou, Jiarui Yao, Di Wu, Zhishang Zhang, Le Tang, Xiaobo Yu, Xiaohong Han, Yuankai Shi

Published in: Cancer Immunology, Immunotherapy | Issue 7/2022

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Abstract

Background

Antibodies targeting programmed cell death-1(PD1) and its ligand (PDL1) have revolutionized cancer therapy. However, little is known about the preexisted anti-PD1/PDL1 autoantibodies (AAbs) distribution in multiple cancer types, nor is their potential biomarker role for anti-PD1 therapy.

Method

Plasma anti-PD1/PDL1 AAb IgG and subclasses (IgG1-4) were detected by enzyme-linked immune sorbent assay (ELISA) in 190 cancer patients, covering 10 cancer types (lung, breast, esophageal, colorectal, liver, prostatic, cervical, ovarian, gastric cancers and lymphoma), the comprehensive correlation of AAbs with multiple clinical parameters was analyzed. We further tested these AAbs in 76 non-small cell lung cancer (NSCLC) samples receiving anti-PD1 therapy, the association of AAbs level with survival was analyzed and validated in an independent cohort (n = 32).

Results

Anti-PD1/PDL1 AAb IgG were globally detected in 10 types of cancer patients. IgG1 and IgG2 were the major subtypes for anti-PD1/PDL1 AAbs. Correlation analysis revealed a distinct landscape between various cancer types. The random forest model indicated that IgG4 subtype was mostly associated with cancer. In discovery cohort of 76 NSCLC patients, high anti-PD1 IgG4 was associated with a reduced overall survival (OS, p = 0.019), not progression-free survival (PFS, p = 0.088). The negative association of anti-PD1 IgG4 with OS was validated in 32 NSCLC patients (p = 0.032).

Conclusion

This study reports for the first time the distribution of preexisted anti-PD1/PDL1 AAb IgG and subclasses across 10 cancer types. Moreover, the anti-PD1 AAb IgG4 subclass was identified to associate with OS, which may serve as a potential biomarker for anti-PD1 therapeutic survival benefit in NSCLC patients.
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Metadata
Title
Anti-PD1/PDL1 IgG subclass distribution in ten cancer types and anti-PD1 IgG4 as biomarker for the long time survival in NSCLC with anti-PD1 therapy
Authors
Qiaoyun Tan
Liyuan Dai
Yanrong Wang
Shuxia Liu
Te Liang
Rongrong Luo
Shasha Wang
Ning Lou
Haizhu Chen
Yu Zhou
Qiaofeng Zhong
Jianliang Yang
Puyuan Xing
Xingsheng Hu
Yutao Liu
Shengyu Zhou
Jiarui Yao
Di Wu
Zhishang Zhang
Le Tang
Xiaobo Yu
Xiaohong Han
Yuankai Shi
Publication date
24-11-2021
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 7/2022
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-021-03106-z

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