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OMIP-106:用于分析急性髓系白血病患者骨髓中检查点抑制网络的 30 色方案

英文原题:OMIP-106: A 30-color panel for analysis of check-point inhibitory networks in the bone marrow of acute myeloid leukemia patients.

PubMed 2024/08/27(内容时间) Cytometry A Q2 · IF 2.9(JCR 2025)

研究概要

急性髓系白血病(AML)是成人中最常见的急性白血病类型。

中文摘要

急性髓系白血病(AML)是成人中最常见的急性白血病类型。尽管医疗护理取得了进展,AML的治疗仍面临诸多挑战,例如治疗相关毒性,限制了高强度化疗的使用,尤其是在老年患者中。目前,多种免疫治疗策略,即CAR-T细胞、BiTEs和免疫检查点抑制剂,正在临床试验中进行测试,以延长AML患者的缓解期并改善其总生存期。然而,早期报告显示这些干预措施仅带来有限的获益,且仅在一部分患者中有效,这表明需要基于免疫学标志物进行更好的患者分层。因此,我们开发并优化了一个30色panel,用于评估效应免疫细胞(NK细胞、T细胞、NKT样T细胞和经典T细胞)对骨髓的浸润,并分析其表型,包括分化状态、抑制性受体(PD-1、TIGIT、Tim3、NKG2A)和激活性受体(DNAM-1、NKG2D)的表达。我们还通过分析抑制性配体如PD-L1、CD112、CD155和CD200的表达,评估CD33+髓系细胞、CD34+CD38-和CD34+CD38+造血干/祖细胞的免疫逃逸表型。我们的panel可作为临床试验中患者分层的宝贵工具,也可用于拓宽我们对AML中检查点抑制网络的理解。

展开英文摘要原文

Acute myeloid leukemia (AML) is the most common form of acute leukemia diagnosed in adults. Despite advances in medical care, the treatment of AML still faces many challenges, such as treatment-related toxicities, that limit the use of high-intensity chemotherapy, especially in elderly patients. Currently, various immunotherapeutic approaches, that is, CAR-T cells, BiTEs, and immune checkpoint inhibitors, are being tested in clinical trials to prolong remission and improve the overall survival of AML patients. However, early reports show only limited benefits of these interventions and only in a subset of patients, showing the need for better patient stratification based on immunological markers. We have therefore developed and optimized a 30-color panel for evaluation of effector immune cell (NK cells, T cells, NKT-like T cells, and classical T cells) infiltration into the bone marrow and analysis of their phenotype with regard to their differentiation, expression of inhibitory (PD-1, TIGIT, Tim3, NKG2A) and activating receptors (DNAM-1, NKG2D). We also evaluate the immune evasive phenotype of CD33 + myeloid cells, CD34 + CD38 - , and CD34 + CD38 + hematopoietic stem and progenitor cells by analyzing the expression of inhibitory ligands such as PD-L1, CD112, CD155, and CD200. Our panel can be a valuable tool for patient stratification in clinical trials and can also be used to broaden our understanding of check-point inhibitory networks in AML.

论文信息

作者
Musil J、Ptacek A、Vanikova S
单位
Department of Immunomonitoring and Flow Cytometry, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.Czechia
文献类型
非美国政府资助研究
期刊
Cytometry. Part A : the journal of the International Society for Analytical Cytology2024 Oct
原文标识
PubMed 39192598 · DOI 10.1002/cyto.a.24892