骨髓中高比例的组织驻留样记忆CD8 T细胞预示急性髓系白血病患者的生存预后较差。
High percentage of bone marrow CD8 tissue-resident-like memory T cells predicts inferior survival in patients with acute myeloid leukemia.
作者信息
Cai Letong, Lai Wenpu, Yao Danlin, Gu Yinfeng, Liang Chaofeng, Liu Lian, Lai Jing, Yu Zhi, Zha Xianfeng, Yu Xibao, Wu Xiuli, Chen Shaohua, Luo Oscar Junhong, Li Yangqiu, Wang Chunyan, Qin Pengfei, Huang Xin, Xu Ling
机构信息
Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Department of Hematology, The First Affiliated Hospital Jinan University, Guangzhou 510632, China.
Department of Systems Biomedical Sciences, School of Medicine, Jinan University, Guangzhou 510632, China.
出版信息
Blood Sci. 2024 Jun 7;6(3):e00194. doi: 10.1097/BS9.0000000000000194. eCollection 2024 Jul.
Tissue-resident memory T (TRM) cells infiltrating solid tumors could influence tumor progression and the response to immune therapies. However, the proportion and prognostic value of TRM cells in the bone marrow (BM) of patients with acute myeloid leukemia (AML) are unclear. In this study, we used flow cytometry to assay the phenotype of 49 BM samples from patients newly diagnosed with AML (ND-AML). We found that the BM CD8 effector memory (TEM) cells highly expressed CD69 (CD8 TRM-like T cells), and their percentage was significantly increased in patients with ND-AML compared with that in healthy individuals (HI). The high percentage of CD8 TRM-like subset was associated with poor overall survival in our ND-AML cohort. The Kaplan-Meier Plotter database verified a significantly reduced survival rate among patients with high expression of CD8 TRM-like T cell characteristic genes (, , and ), especially the M4 and M5 subtypes. Phenotypic analysis revealed that the BM CD8 TRM-like subpopulation exhibited exhausted T cell characteristics, but its high expression of CD27 and CD28 and low expression of CD57 suggested its high proliferative potential. The single-cell proteogenomic dataset confirmed the existence of TRM-like CD8 T cells in the BM of patients with AML and verified the high expression of immune checkpoints and costimulatory molecules. In conclusion, we found that the accumulation of BM CD8 TRM-like cells could be an immune-related survival prediction marker for patients with AML.
浸润实体瘤的组织驻留记忆T(TRM)细胞可影响肿瘤进展及对免疫治疗的反应。然而,急性髓系白血病(AML)患者骨髓(BM)中TRM细胞的比例及预后价值尚不清楚。在本研究中,我们采用流式细胞术检测了49例新诊断AML(ND-AML)患者BM样本的表型。我们发现BM CD8效应记忆(TEM)细胞高表达CD69(CD8 TRM样T细胞),与健康个体(HI)相比,ND-AML患者中其百分比显著增加。在我们的ND-AML队列中,CD8 TRM样亚群的高百分比与较差的总生存期相关。Kaplan-Meier Plotter数据库证实,CD8 TRM样T细胞特征基因( 、 和 )高表达的患者生存率显著降低,尤其是M4和M5亚型。表型分析显示,BM CD8 TRM样亚群表现出耗竭T细胞特征,但其CD27和CD28高表达及CD57低表达提示其具有高增殖潜力。单细胞蛋白质基因组数据集证实了AML患者BM中存在TRM样CD8 T细胞,并验证了免疫检查点和共刺激分子的高表达。总之,我们发现BM CD8 TRM样细胞的积累可能是AML患者免疫相关的生存预测标志物。