Abstract

BackgroundOne of the crucial functions of the immune system is to prevent tumorigenesis, yet cancer occurs when malignant cells manage to evade immune surveillance via multiple strategies. Accordingly, this study aimed at assessing the potential significance of the novel immune checkpoint B and T lymphocyte attenuator (BTLA) as a prognostic marker in acute myeloid leukemia (AML), in addition to how it relates to response to treatment and patients’ survival. Thus, mRNA expression of BTLA was investigated on peripheral blood in 60 AML patients and 15 healthy controls.ResultsBTLA expression was found to be significantly elevated (p = 0.024) in the tested AML cases in comparison with healthy controls. Moreover, BTLA was over-expressed in the CD13, CD33, and HLA-DR positive cases as compared to their negative counterparts (p = 0.003; p < 0.001, and p = 0.001, respectively), and cases showing BTLA over-expression had significantly poorer overall survival times (p = 0.001) as confirmed by Kaplan–Meier survival analysis.ConclusionThese observations suggest that BTLA over-expression may be associated with reduced immunity against tumors and could be recommended as a promising biomarker for unfavorable prognosis in AML.

Highlights

  • One of the crucial functions of the immune system is to prevent tumorigenesis, yet cancer occurs when malignant cells manage to evade immune surveillance via multiple strategies

  • Co-stimulatory and co-inhibitory mediators adjust T-cell proliferation, half-life, and cytokine release and enable effective T-cell responses to malignancy, yet controlling autoimmunity [5]. The balance between both these co-stimulatory and co-inhibitory signaling pathways acts as a molecular switch between activation and inhibition [6]. This balance may be interrupted by continual antigen stimulation, as well as release of mediators, that suppress the immune response in the tumor microenvironment, causing T-cell dysfunction, called “T-cell exhaustion,” leading to its failure of Radwan et al Egypt J Med Hum Genet (2021) 22:78 cancer eradication responses [7]

  • B and T lymphocyte attenuator (BTLA) expression levels were higher in acute myeloid leukemia (AML) patients with unfavorable prognosis as compared to AML patients with favorable prognosis

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Summary

Introduction

One of the crucial functions of the immune system is to prevent tumorigenesis, yet cancer occurs when malignant cells manage to evade immune surveillance via multiple strategies. Co-stimulatory and co-inhibitory mediators adjust T-cell proliferation, half-life, and cytokine release and enable effective T-cell responses to malignancy, yet controlling autoimmunity [5] The balance between both these co-stimulatory and co-inhibitory signaling pathways acts as a molecular switch between activation and inhibition [6]. This balance may be interrupted by continual antigen stimulation, as well as release of mediators, that suppress the immune response in the tumor microenvironment, causing T-cell dysfunction, called “T-cell exhaustion,” leading to its failure of Radwan et al Egypt J Med Hum Genet (2021) 22:78 cancer eradication responses [7]. The expanding immunotherapeutic approaches markedly offer several treatment options but should be engaged sensibly and cautiously

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