Higher PD-1 expression concurrent with exhausted CD8+ T cells in patients with de novo acute myeloid leukemia

Objective： To investigate the association between the T cell inhibitory receptor programmed death 1（PD-1）and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia（AML） and AML in complete remission（CR）.Methods：Surface expression of PD-1 and the exhaustion and immunosenescence markers CD244 and CD57 on CD3＋,CD4＋ and CD8＋ T cells from peripheral blood samples from 20 newly diagnosed,untreated AML patients and 10 cases with AML in CR was analyzed by flow cytometry.Twenty-three healthy individuals served as control.Results：A significantly higher percentage of PD-1＋ cells were found for CD3＋ T cells in the de novo AML group compared with healthy controls.In addition,an increased level of PD-1＋ CD8＋ T cells,but not PD-1＋ CD4＋,was found for CD3＋ T cells in the de novo AML and AML-CR samples.A higher percentage of CD244＋ CD4＋,CD244＋ CD8＋,CD57＋ CD4＋ and CD57＋ CD8＋ T cells was found in CD3＋ T cells in samples from those with de novo AML compared with those from healthy controls.Strong increased PD-1＋ CD244＋ and PD-1＋ CD57＋ coexpression was found for CD4＋ and CD8＋ T cells in the de novo AML group compared with healthy controls.Conclusions：We characterized the major T cell defects,including co-expression of PD-1 and CD244,CD57-exhausted T cells in patients with de novo AML,and found a particular influence on CD8＋ T cells,suggesting a poor anti-leukemia immune response in these patients.

High percentage of bone marrow CD8^(+)tissue-resident-like memory T cells predicts inferior survival in patients with acute myeloid leukemia

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(CD8A,CD69,and TOX),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.