Characterization of the Bone Marrow Lymphoid Microenvironment and Discovery of Prognostic Immune-Related Factors in Acute Myeloid Leukemia

急性髓系白血病骨髓淋巴微环境的特征分析及预后免疫相关因子的发现

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Abstract

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.

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