Abstract
In the new world of medicine, one of the main concerns in the field of infectious diseases has been focused on Human T-cell Leukemia Virus type 1 (HTLV-1). During the infection, lymphocyte inhibitory receptors (LIRs) play a prominent role in the occurrence of adult T-cell leukemia/lymphoma (ATLL). These receptors include LAG3, PD-1, TIGIT, CD160, TIM3, and 2B4. First, we have collected all microarray information on the profile of HTLV-1 infected patients from the Gene Expression Omnibus (http://www.ncbi.nlm.gov/geo) database until March 2020, in order to identify the microarray related to evolutionary development of LTRs during various phases of HTLV-1 infection in human peripheral blood CD4+ T cells by searching for keywords such as “Human T-lymphotropic virus type I (HTLV-1)”, “Homo sapiens”, “ATLL”, and “Whole genome sequencing”. Considering the main goal of the study, we have only assessed data related to Homo sapiens particularly CD4+ T cell lineage from human subjects infected with HTLV-1. We evaluated these receptors in ATLL patients compared to healthy control (HC) individuals and HTLV-1 infected-asymptomatic carriers (ASCs). Out of all 18 identified records, we only selected and analyzed three studies: GSE19080, GSE33615, and GSE57259, which satisfied inclusion criteria with proper quality analysis of ATLL vs. normal, ATLL vs. asymptomatic carrier as well as asymptomatic carrier vs. normal. Unfortunately, we could not analyze various stages of ATLL malignancy (acute, lymphomatous, chronic and smoldering) in all included studies due to the lack of sufficient information. Finally, based on Benjamini–Hochberg False discovery rate (FDR), the differentially expressed genes (DEGs) were selected for several categories. Hence, for the first time we demonstrated that the expression rate of LIRs in ATLL group was higher than either in asymptomatic carrier or healthy donor groups. As a conclusion, it seems that the blockade of LIRs has a pivotal role in diagnostics and treatment of ATLL malignancy.
Highlights
In recent years, it has been demonstrated that high expression of inhibitor receptors on lymphocytes leads to modulation of function of co-stimulatory receptors and decreased T cell activity, tissue damage, and autoimmunity [1, 33]
The aim of this study was to investigate the differences of expression of lymphocyte inhibitory receptors (LIRs) genes such as LAG3, PD-1, T-Cell Immunoglobulin and ITIM Domain (TIGIT), CD160, TIM3, and 2B4 in adult T-cell leukemia/lymphoma (ATLL) patients compared to healthy control (HC) individuals and Human T-cell leukemia virus type 1 (HTLV-1) infected-asymptomatic carriers (ASCs)
The analysis of GSE33615 study showed that expression of LIRs in particular PD-1 and LAG3 genes was significantly related to severity of the disease (p value < 0.001)
Summary
It has been demonstrated that high expression of inhibitor receptors on lymphocytes leads to modulation of function of co-stimulatory receptors and decreased T cell activity, tissue damage, and autoimmunity [1, 33]. According to in vitro evidence, about 24 h after stimulation of lymphocytes, lymphocyte inhibitory receptors (LIRs) begin to express and reach to their highest levels after 48 h [31] It seems that long stimulation of lymphocytes increases the expression of LIRs genes, which in turn leads to the T cells dysfunction, and cancer [26, 33]. Like hepatitis C virus, Human T-cell leukemia virus type 1 (HTLV-1) is one of the most important single-stranded RNA viruses [2, 12]. Once it enters human circulatory system, HTLV-1 creates persistent infection and chronic inflammation through inhibition and escape mechanisms from facing immune responses. The aim of this study was to investigate the differences of expression of LIRs genes such as LAG3, PD-1, TIGIT, CD160, TIM3, and 2B4 in ATLL patients compared to healthy control (HC) individuals and HTLV-1 infected-asymptomatic carriers (ASCs)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
