Kim Yoon-Ju, Kwag Daehun, Kim Bo-Reum, Son Hyunsong, Park Silvia, Kim Hee-Je, Cho Byung-Sik
Department of Biomedicine & Health Sciences, Graduate Program for Future Medical Research Leaders, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Department of Hematology, Catholic Hematology Hospital, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Int J Mol Sci. 2024 Dec 4;25(23):13039. doi: 10.3390/ijms252313039.
Given the limited comprehensive data on the bone marrow (BM) immune environment in acute myeloid leukemia (AML), we analyzed the distribution and phenotype of T cell subsets, including γδ T cells, and their immune checkpoint (IC) ligands on blasts. We performed multiparametric flow cytometry with BM samples taken from 89 AML patients at the time of diagnosis, remission, and relapse/refractory status after chemotherapy and 13 healthy controls (HCs) to identify immune-related risk factors. Compared to the HCs, the T cells of the AML patients exhibited exhausted features including higher TIGIT levels and similar levels of PD-1 and TIM-3. The γδ T cells were exhausted by the upregulation of TIGIT and/or TIM-3 and downregulation of NKG2D and NKp30, with different patterns in the Vδ1 and Vδ2 subtypes. A successful chemotherapeutic response partially restored the exhausted phenotypes of the T cell subsets. The simultaneous analysis of IC receptors on the T cell subsets and their ligands on blasts showed the prognostic value of a specific IC receptor-ligand pair and the feasibility of risk stratification based on their diverse patterns. Our findings clarified the BM T cell landscape in AML, unveiling the prognostic value of γδ T cells in both diagnosis and remission predictions.
鉴于急性髓系白血病（AML）中关于骨髓（BM）免疫环境的全面数据有限，我们分析了T细胞亚群（包括γδ T细胞）的分布和表型，以及原始细胞上的免疫检查点（IC）配体。我们对89例AML患者在诊断时、缓解期以及化疗后的复发/难治状态采集的骨髓样本，以及13名健康对照（HC）进行了多参数流式细胞术分析，以确定免疫相关风险因素。与HC相比，AML患者的T细胞表现出耗竭特征，包括更高的TIGIT水平以及相似水平的PD-1和TIM-3。γδ T细胞因TIGIT和/或TIM-3上调以及NKG2D和NKp30下调而耗竭，Vδ1和Vδ2亚型呈现不同模式。成功的化疗反应部分恢复了T细胞亚群的耗竭表型。对T细胞亚群上的IC受体及其原始细胞上的配体进行同步分析，显示了特定IC受体-配体对的预后价值以及基于其不同模式进行风险分层的可行性。我们的研究结果阐明了AML中的骨髓T细胞格局，揭示了γδ T细胞在诊断和缓解预测中的预后价值。
