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

Int J Mol Sci. 2024 Dec 4;25(23):13039. doi: 10.3390/ijms252313039.

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.

Keywords: T cell exhaustion; acute myeloid leukemia; immune checkpoint receptor; prognosis; γδ T cells.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow* / immunology
  • Bone Marrow* / metabolism
  • Bone Marrow* / pathology
  • Female
  • Hepatitis A Virus Cellular Receptor 2 / metabolism
  • Humans
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / immunology
  • Leukemia, Myeloid, Acute* / metabolism
  • Leukemia, Myeloid, Acute* / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Tumor Microenvironment* / immunology
  • Young Adult

Substances

  • Hepatitis A Virus Cellular Receptor 2
  • HAVCR2 protein, human
  • Receptors, Antigen, T-Cell, gamma-delta