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免疫检查点抑制剂治疗的癌症患者免疫相关不良反应的预测生物标志物。

Predictive biomarkers for immune-related adverse events in cancer patients treated with immune-checkpoint inhibitors.

机构信息

Department of Oncology, Beijing Friendship Hospital, Capital Medical University, #95 Yong An Road, Xicheng District, Beijing, China.

Radiotherapy Department, Shijingshan Teaching Hospital of Capital Medical University Beijing, #24 Shijingshan Road, Shijingshan District, Beijing, 100040, China.

出版信息

BMC Immunol. 2024 Jan 24;25(1):8. doi: 10.1186/s12865-024-00599-y.


DOI:10.1186/s12865-024-00599-y
PMID:38267897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10809515/
Abstract

PURPOSE: The objective of this study was to identify potential predictors of immune-related adverse events (irAEs) in cancer patients receiving immune checkpoint inhibitor therapy among serum indexes, case data, and liquid biopsy results. METHODS: We retrospectively analyzed 418 patients treated with anti-programmed cell death 1(PD-1)/PD-1 ligand (PD-L1) inhibitors from January 2018 to May 2022 in our cancer center. We identified factors that correlated with the occurrence of irAEs and evaluated associations between irAEs and anti-PD-1/PD-L1 inhibitor responses. RESULTS: The incidence of irAEs was 42.1%, and pneumonitis (9.1%), thyroid toxicity (9.1%), cardiotoxicity (8.1%), and dermatologic toxicity (6.9%) were the four most common irAEs. Multivariate logistic analysis identified female sex, antibiotic use, higher post-treatment neutrophil-to-lymphocyte ratio (NLR), and higher baseline circulating tumor cell (CTC) level, as predictive biomarkers for the occurrence of irAEs. A lower baseline prognostic nutritional index (PNI), body mass index (BMI) ≥ 25 kg/m, and higher post-treatment lactate dehydrogenase (LDH) level were predictive factors for more severe irAEs (higher severity grade). Patients without irAEs had better overall survival than those with irAEs. Specifically, pneumonitis and cardiotoxicity were found to be significant predictors of poor prognosis in the irAE subgroup with different organ-related irAEs. Low-dose steroid (dexamethasone 10 mg) treatment had no significant effect on outcomes. CONCLUSIONS: Gender, antibiotic use, post-treatment NLR, and baseline CTC level are potential predictive biomarkers of irAEs, while baseline PNI, BMI, and post-treatment LDH may predict the severity of irAEs. The predictive effect of irAE occurrence on survival benefit may depend on the type of irAE.

摘要

目的:本研究旨在从血清指标、病例数据和液体活检结果中,确定接受免疫检查点抑制剂治疗的癌症患者发生免疫相关不良事件(irAE)的潜在预测因素。

方法:我们回顾性分析了 2018 年 1 月至 2022 年 5 月在我院癌症中心接受抗程序性死亡 1(PD-1)/PD-1 配体(PD-L1)抑制剂治疗的 418 例患者。我们确定了与 irAE 发生相关的因素,并评估了 irAE 与抗 PD-1/PD-L1 抑制剂反应之间的关系。

结果:irAE 的发生率为 42.1%,最常见的 4 种 irAE 为肺炎(9.1%)、甲状腺毒性(9.1%)、心脏毒性(8.1%)和皮肤毒性(6.9%)。多变量 logistic 分析确定女性、使用抗生素、治疗后中性粒细胞与淋巴细胞比值(NLR)升高和基线循环肿瘤细胞(CTC)水平升高是 irAE 发生的预测生物标志物。较低的基线预后营养指数(PNI)、体质量指数(BMI)≥25kg/m 和较高的治疗后乳酸脱氢酶(LDH)水平是 irAE 更严重的预测因素(更高的严重程度等级)。无 irAE 患者的总生存优于有 irAE 患者。具体来说,在不同器官相关 irAE 的 irAE 亚组中,肺炎和心脏毒性被发现是预后不良的显著预测因子。低剂量类固醇(地塞米松 10mg)治疗对结局没有显著影响。

结论:性别、抗生素使用、治疗后 NLR 和基线 CTC 水平是 irAE 的潜在预测生物标志物,而基线 PNI、BMI 和治疗后 LDH 可能预测 irAE 的严重程度。irAE 发生对生存获益的预测作用可能取决于 irAE 的类型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/75dff9ebe16e/12865_2024_599_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/ca7f9996e05f/12865_2024_599_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/adea255c3f88/12865_2024_599_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/119dfa4e6311/12865_2024_599_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/5d0117f944c9/12865_2024_599_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/c76cec260777/12865_2024_599_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/600bc1c92522/12865_2024_599_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/75dff9ebe16e/12865_2024_599_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/ca7f9996e05f/12865_2024_599_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/adea255c3f88/12865_2024_599_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/119dfa4e6311/12865_2024_599_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/5d0117f944c9/12865_2024_599_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/c76cec260777/12865_2024_599_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/600bc1c92522/12865_2024_599_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baa/10809515/75dff9ebe16e/12865_2024_599_Fig7_HTML.jpg

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[3]
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Am J Transl Res. 2025-7-15

[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Association of Body Mass Index With the Safety Profile of Nivolumab With or Without Ipilimumab.

JAMA Oncol. 2023-1-1

[2]
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Nat Rev Clin Oncol. 2022-12

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Front Immunol. 2022

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Front Immunol. 2022

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Pan-cancer analysis reveals sex-specific signatures in the tumor microenvironment.

Mol Oncol. 2022-6

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Prognostic effect of body mass index in patients with advanced NSCLC treated with chemoimmunotherapy combinations.

J Immunother Cancer. 2022-2

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