外周血淋巴细胞分化模式与非小细胞肺癌免疫检查点阻断治疗反应/结局的相关性:一项回顾性研究。

Peripheral blood lymphocytes differentiation patterns in responses / outcomes to immune checkpoint blockade therapies in non-small cell lung cancer: a retrospective study.

机构信息

Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

BMC Cancer. 2023 Jan 25;23(1):83. doi: 10.1186/s12885-023-10502-4.

Abstract

OBJECTIVES

Programmed Cell Death-1/ Programmed Death-ligand 1 (PD-1 / PD-L1) inhibitor therapies targeting immunocytes induce persistent tumor remission in various cancers. However, the appropriate biomarkers for the therapeutic efficacy of PD-L1 and PD-1 blockade remain elusive.

MATERIALS AND METHODS

For a comprehensive analysis of peri-treatment lymphocyte differentiation, in the current study, we enrolled 146 non-small cell lung cancer patients who received α-PD-1 therapies for exploring the peripheral blood lymphocyte differentiation pattern at baseline and post-treatment (dynamic changes) by flow cytometry.

RESULTS

At baseline, CD4 / CD8 T cell ratio predicts good responses and outcomes, but activated T cell and cytotoxic T cell counts predict poor responses and outcomes. And for dynamic changes, after 6 weeks of immune checkpoint blockade (ICB) treatment, compared with baseline level, the elevation of total T and B cell counts indicate poor responses, and total T and T cell counts indicate poor prognosis while activated T cell predicts good prognosis. And after 12 weeks, elevated total lymphocyte, cytotoxic T cell counts, and decreased total T cell counts and CD4 / CD8 T cell ratio predict good responses / outcomes. Our clinical predicting model shows good performance in predicting ICB treatment responses / outcomes.

CONCLUSION

Patients with favorable clinical responses / outcomes have distinctive peripheral blood immunocyte differentiation characteristics, indicating the potential of utilizing the peripheral immunocyte differentiation patterns for predicting ICB responses / outcomes.

摘要

目的

针对免疫细胞的程序性细胞死亡受体-1/程序性死亡配体 1(PD-1/PD-L1)抑制剂治疗在多种癌症中诱导持久的肿瘤缓解。然而,针对 PD-L1 和 PD-1 阻断治疗疗效的适当生物标志物仍难以捉摸。

材料和方法

为了全面分析治疗前淋巴细胞分化,在目前的研究中,我们招募了 146 名接受 α-PD-1 治疗的非小细胞肺癌患者,通过流式细胞术探索基线和治疗后(动态变化)的外周血淋巴细胞分化模式。

结果

基线时,CD4/CD8 T 细胞比值预测良好的反应和结局,但活化 T 细胞和细胞毒性 T 细胞计数预测不良的反应和结局。对于动态变化,在免疫检查点阻断(ICB)治疗 6 周后,与基线水平相比,总 T 和 B 细胞计数的升高预示着不良反应,总 T 和 T 细胞计数预示着不良预后,而活化 T 细胞预示着良好的预后。在 12 周后,总淋巴细胞、细胞毒性 T 细胞计数升高,总 T 细胞计数和 CD4/CD8 T 细胞比值降低预示着良好的反应/结局。我们的临床预测模型在预测 ICB 治疗反应/结局方面表现出良好的性能。

结论

具有良好临床反应/结局的患者具有独特的外周血免疫细胞分化特征,表明利用外周免疫细胞分化模式预测 ICB 反应/结局的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b3/9875514/9be77d85b3e7/12885_2023_10502_Fig1_HTML.jpg

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