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癌症干细胞与重编程CD3CD8 T细胞的体外研究:探寻小细胞肺癌的个性化诊断与靶向治疗(一项初步研究的经验)

In Vitro Study of Cancer Stem Cells and Reprogrammed CD3CD8 T Cells: the Search for Personalized Diagnostics and Targeted Treatment of Small Cell Lung Cancer (Experience of a Pilot Study).

作者信息

Skurikhin E G, Ermakova N N, Zhukova M A, Pan E S, Kubatiev A A, Morozov S G, Dygai A M

机构信息

Institute of General Pathology and Pathophysiology, Moscow, Russia.

出版信息

Bull Exp Biol Med. 2025 Mar;178(5):631-636. doi: 10.1007/s10517-025-06388-w. Epub 2025 Apr 28.

Abstract

The content of cancer stem cells and CD3CD8 T cells in the blood of a patient with small cell lung cancer (SCLC) and chronic obstructive pulmonary disease (COPD) was evaluated. In vitro analysis of tumorospheres allowed us to characterize circulating tumor stem cells in the blood of patients at risk. The fundamental possibility of reprogramming exhausted CD3CD8 T cells (rCD3CD8T) of a patient with SCLC and COPD using a mitogen-activated protein kinase inhibitor (iMEK) and human monoclonal antibody nivolumab was demonstrated. Target cell elimination by rCD3CD8T was achieved by treatment with autologous cancer cell and stem cancer cell lysate in vitro. Thus, blockade of the MAPK/ERK signaling pathway and the PD-1/PD-L1 checkpoints may be used to overcome exhaustion and enhance cytotoxicity of CD3CD8 T cells in patients with SCLC and COPD.

摘要

评估了一名小细胞肺癌(SCLC)合并慢性阻塞性肺疾病(COPD)患者血液中癌症干细胞和CD3CD8 T细胞的含量。对肿瘤球进行体外分析使我们能够表征有风险患者血液中的循环肿瘤干细胞。证明了使用丝裂原活化蛋白激酶抑制剂(iMEK)和人源单克隆抗体纳武单抗对SCLC合并COPD患者的耗竭性CD3CD8 T细胞(rCD3CD8T)进行重编程的基本可能性。通过体外使用自体癌细胞和癌干细胞裂解物处理实现了rCD3CD8T对靶细胞的清除。因此,MAPK/ERK信号通路和PD-1/PD-L1检查点的阻断可用于克服SCLC合并COPD患者CD3CD8 T细胞的耗竭并增强其细胞毒性。

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