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    • Comprehensive Analysis of the Immune Pattern of T Cell Subsets in Chronic Myeloid Leukemia Before and after TKI Treatment

    Danlin Yao,Jing Lai,Yuhong Lu,Jun Zhong,Xianfeng Zha,Xin Huang,Lian Liu,Xiangbo Zeng,Shaohua Chen,Jianyu Weng,Xin Du,Yangqiu Li,Ling Xu

    Frontiers in immunology（2023）SCI 2区

    Jinan Univ | Guangdong Prov Peoples Hosp

    Cited 5|Views1
    Abstract
    BackgroundImmunological phenotypes and differentiation statuses commonly decide the T cell function and anti-tumor ability. However, little is known about these alterations in CML patients. MethodHere, we investigated the immunologic phenotypes (CD38/CD69/HLA-DR/CD28/CD57/BTLA/TIGIT/PD-1) of T subsets (TN, TCM, TEM, and TEMRA) in peripheral blood (PB) and bone marrow (BM) from de novo CML patients (DN-CML), patients who achieved a molecular response (MR) and those who failed to achieve an MR (TKI-F) after tyrosine kinase inhibitor (TKI) treatment using multicolor flow cytometry. ResultsCD38 or HLA-DR positive PB CD8+TN and TCM cells decreased in the DN-CML patients and this was further decreased in TKI-F patients. Meanwhile, the level of PD-1 elevated in CD8+ TEM and TEMRA cells from PB in all groups. Among BM sample, the level of HLA-DR+CD8+TCM cells significantly decreased in all groups and CD8+TEMRA cells from TKI-F patients exhibited increased level of TIGIT and CD8+ tissue-residual T cells (TRM) from DN-CML patients expressed a higher level of PD-1 and TIGIT. Lastly, we found a significantly decreased proportion of CD86+ dendritic cells (DCs) and an imbalanced CD80/CD86 in the PB and BM of DN-CML patients, which may impair the activation of T cells. ConclusionIn summary, early differentiated TN and TCM cells from CML patients may remain in an inadequate activation state, particularly for TKI-F patients. And effector T cells (TEM, TEMRA and TRM) may be dysfunctional due to the expression of PD-1 and TIGIT in CML patients. Meanwhile, DCs cells exhibited the impairment of costimulatory molecule expression in DN-CML patients. Those factors may jointly contribute to the immune escape in CML patients.
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    T cell subsets,CML,bone marrow microenvironment,immunological phenotypes,tyrosine kinase inhibitor
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    【要点】：本研究通过多色流式细胞术分析CML患者接受TKI治疗前后的T细胞亚群免疫表型，发现T细胞亚群的改变与免疫逃逸相关，为CML患者的免疫治疗提供了新的视角。
    

    【方法】：使用多色流式细胞术对初诊CML患者、达到分子反应的患者以及TKI治疗失败患者的PB和BM样本中的T细胞亚群进行免疫表型分析。
    

    【实验】：通过检测CD38/CD69/HLA-DR/CD28/CD57/BTLA/TIGIT/PD-1等分子的表达，发现DN-CML患者和TKI-F患者的PB CD8+TN和TCM细胞CD38或HLA-DR阳性率降低，而所有组别中PB CD8+TEM和TEMRA细胞的PD-1水平升高。BM样本中，HLA-DR+CD8+TCM细胞水平显著降低，TKI-F患者的CD8+TEMRA细胞TIGIT水平升高，DN-CML患者的CD8+组织残留T细胞PD-1和TIGIT表达升高。DN-CML患者PB和BM中的CD86+树突状细胞比例显著降低，CD80/CD86比值失衡。
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