Characterization of Immune Dysfunction and Identification of Prognostic Immune-Related Risk Factors in Acute Myeloid Leukemia

Abstract

Purpose: This study aims to provide comprehensive insights into longitudinal immune landscape in acute myeloid leukemia (AML) development and treatment, which may contribute to predict prognosis and guide clinical decisions.Experimental Design: Periphery blood samples from 79 patients with AML (at diagnosis or/and after chemotherapy or at relapse) and 24 healthy controls were prospectively collected. We performed phenotypic and functional analysis of various lymphocytes through multiparametric flow cytometry and investigated prognostic immune-related risk factors.Results: Immune defects in AML were reflected in T and natural killer (NK) cells, whereas B-cell function remained unaffected. Both CD8 þ T and CD4 þ T cells exhibited features of senescence and exhaustion at diagnosis. NK dysfunction was supported by excessive maturation and downregulation of NKG2D and NKP30. Diseased gd T cells demonstrated a highly activated or even exhausted state through PD-1 upregulation and NKG2D downregulation. Effective therapeutic response following chemotherapy correlated with T and NK function restoration. Refractory and relapsed patients demonstrated even worse immune impairments, and selective immune signatures apparently correlated clinical outcomes and survival. PD-1 expression in CD8 þ T cells was independently predictive of poor overall survival and event-free survival.Conclusions: T-cell senescence and exhaustion, together with impaired NK and gd T-cell function, are dominant aspects involved in immune dysfunction in AML. Noninvasive immune testing of blood samples could be applied to predict therapeutic reactivity, high risk for relapse, and unfavorable prognosis.

Cancer history is an independent risk factor for mortality in hospitalized COVID-19 patients: a propensity score-matched analysis

“…Hematological malignancies, such as leukemia and lymphoma, can affect the immune system directly. T cell senescence and exhaustion are dominant aspects involved in immune dysfunction in hematological malignancies [28]. The dysregulation of the immune response in severe patients with COVID-19 has been emphasized, while the recruitment of immune cell populations may play a crucial role in the recovery of COVID-19 infection [28,29].…”

Characteristic of TIGIT and DNAM-1 Expression on Foxp3+ γδ T Cells in AML Patients

“…γδ Tregs exert their suppressive properties through a host of tolerogenic enzymatic pathways and cytokines and the expression of multiple inhibitory receptors [19]. Recent research has reported that γδ T cells exhibit an exhausted state through PD-1 upregulation in AML patients at diagnosis, and whether there is correlation with other immune checkpoint proteins, such as TIGIT and γδ Treg cells in AML remains unclear [20]. Here, we determined the characteristics of the paired receptors TIGIT and DNAM-1 on Foxp3+ γδ Treg cells in AML patients with different clinical statuses and discuss their influence on clinical outcome.…”

Bone marrow infiltrated natural killer cells predicted the anti-leukemia activity of MCL1 or BCL2 inhibitors in acute myeloid leukemia

“…The importance of NK ratio in BM of AML patients has generated tremendous interest in understanding its role in disease management. Immune dysfunction could predict therapeutic reactivity and unfavorable prognosis [5]. By analyzing the types and expression abundance of ligands related to NK function expressed in tumor cells, we first proposed that the proportion of NK cells in the BM of AML patients could predict the prognosis of patients.…”

“…The immune dysfunction recently has been considered as a risk factor in AML and predicted poor prognosis [5]. Next, we utilized Cibersort to deconvolute the geneexpression data of 713 newly diagnosed AML (ND-AML) patients (140 patients as Training cohort and 573 patients as Validation cohort) and generated a gene matrix with a signature of more than 10 immune cell subtypes (Table S2 and S3).…”