抗 PD1/PDL1 IgG 亚类在 10 种癌症类型中的分布和抗 PD1 IgG4 作为抗 PD1 治疗 NSCLC 长期存活的生物标志物,Cancer Immunology, Immunotherapy

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抗 PD1/PDL1 IgG 亚类在 10 种癌症类型中的分布和抗 PD1 IgG4 作为抗 PD1 治疗 NSCLC 长期存活的生物标志物
Cancer Immunology, Immunotherapy ( IF 4.6 ) Pub Date : 2021-11-24 , DOI: 10.1007/s00262-021-03106-z
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

背景

针对程序性细胞死亡 1 (PD1) 及其配体 (PDL1) 的抗体已经彻底改变了癌症治疗。然而，人们对多种癌症类型中预先存在的抗 PD1/PDL1 自身抗体 (AAb) 分布知之甚少，它们在抗 PD1 治疗中的潜在生物标志物作用也知之甚少。

方法

采用酶联免疫吸附试验 (ELISA) 方法检测了 190 名癌症患者的血浆抗 PD1/PDL1 AAb IgG 及其亚类 (IgG1-4)，涵盖 10 种癌症类型（肺癌、乳腺癌、食管癌、结直肠癌、肝癌、前列腺癌、宫颈癌）、卵巢癌、胃癌和淋巴瘤），分析了AAbs与多个临床参数的综合相关性。我们在 76 个接受抗 PD1 治疗的非小细胞肺癌 (NSCLC) 样本中进一步测试了这些 AAbs，在一个独立队列 ( n = 32) 中分析和验证了 AAbs 水平与存活率的关联。

结果

在全球 10 种癌症患者中检测到抗 PD1/PDL1 AAb IgG。IgG1 和 IgG2 是抗 PD1/PDL1 AAb 的主要亚型。相关性分析揭示了各种癌症类型之间的独特景观。随机森林模型表明 IgG4 亚型主要与癌症相关。在 76 名 NSCLC 患者的发现队列中，高抗 PD1 IgG4 与降低的总生存期（OS，p = 0.019）相关，而不是无进展生存期（PFS， p = 0.088）。在 32 名 NSCLC 患者中验证了抗 PD1 IgG4 与 OS 的负相关（p = 0.032）。

结论

这项研究首次报告了 10 种癌症类型中预先存在的抗 PD1/PDL1 AAb IgG 和亚类的分布情况。此外，抗 PD1 AAb IgG4 亚类被确定与 OS 相关，这可能作为 NSCLC 患者抗 PD1 治疗生存获益的潜在生物标志物。

"点击查看英文标题和摘要"

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

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.

更新日期：2021-11-24

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