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外周血 CD4 记忆 T 细胞预测免疫检查点抑制剂治疗非小细胞肺癌患者的疗效。

Peripheral CD4 memory T cells predict the efficacy of immune checkpoint inhibitor therapy in patients with non-small cell lung cancer.

机构信息

First Department of Internal Medicine, Toyama University Hospital, Toyama, Japan.

Department of Clinical Oncology, Toyama University Hospital, Toyama, Japan.

出版信息

Sci Rep. 2023 Jul 4;13(1):10807. doi: 10.1038/s41598-023-37736-3.

DOI:10.1038/s41598-023-37736-3
PMID:37402763
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10319808/
Abstract

Immune checkpoint inhibitors have significantly improved the prognosis in patients with non-small cell lung cancer, compared with cytotoxic agents. However, the prediction of treatment response is often difficult, even after assessing the tumor programmed death-ligand 1 expression. We conducted this observational study to analyze the association between the differentiation of peripheral CD4 + T cells and the efficacy of immune checkpoint inhibitor therapy. We enrolled patients who were diagnosed with non-small cell lung cancer and received immune checkpoint inhibitor therapy between 2020 and 2022. Blood samples were collected at the start of immune checkpoint inhibitor therapy, and the expressions of PD-1, CCR7, and CD45RA in peripheral CD4 + T cells were analyzed by flow cytometry. The association between the findings of flow cytometry and survival after the initiation of the immune checkpoint inhibitor therapy was evaluated. Forty patients with non-small cell lung cancer were enrolled. The Cox proportional hazards model showed that an increased proportion of CD45RA-CD4 + T cells was associated with a reduced risk of progression after adjustment for performance status, tumor programmed death-ligand 1 expression level, mutation status of the epidermal growth factor receptor gene, and combined therapy with cytotoxic agents. The present study showed that the proportion of peripheral CD45RA- CD4 + T cells was associated with progression-free survival after the initiation of immune checkpoint inhibitor therapy, independent of several clinical factors.

摘要

免疫检查点抑制剂与细胞毒药物相比,显著改善了非小细胞肺癌患者的预后。然而,即使在评估肿瘤程序性死亡配体 1 表达后,治疗反应的预测也常常很困难。我们进行了这项观察性研究,以分析外周 CD4+T 细胞分化与免疫检查点抑制剂治疗疗效之间的关系。我们招募了 2020 年至 2022 年间被诊断为非小细胞肺癌并接受免疫检查点抑制剂治疗的患者。在开始免疫检查点抑制剂治疗时采集血样,并通过流式细胞术分析外周 CD4+T 细胞中 PD-1、CCR7 和 CD45RA 的表达。评估流式细胞术结果与免疫检查点抑制剂治疗开始后生存之间的关系。共纳入 40 例非小细胞肺癌患者。Cox 比例风险模型显示,在调整体能状态、肿瘤程序性死亡配体 1 表达水平、表皮生长因子受体基因突变状态以及与细胞毒药物联合治疗后,CD45RA-CD4+T 细胞比例增加与进展风险降低相关。本研究表明,外周 CD45RA-CD4+T 细胞比例与免疫检查点抑制剂治疗开始后的无进展生存期相关,独立于多个临床因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5f/10319808/55b7155a5d6f/41598_2023_37736_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5f/10319808/b9a4215465d3/41598_2023_37736_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5f/10319808/b50a330b95ff/41598_2023_37736_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5f/10319808/5809654063af/41598_2023_37736_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5f/10319808/55b7155a5d6f/41598_2023_37736_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5f/10319808/b9a4215465d3/41598_2023_37736_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5f/10319808/b50a330b95ff/41598_2023_37736_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5f/10319808/5809654063af/41598_2023_37736_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5f/10319808/55b7155a5d6f/41598_2023_37736_Fig4_HTML.jpg

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