CD8+T-cells Co-expressing PD-1 and TIGIT Are Highly Frequent in Chronic Lymphocytic Leukemia

Reza  Hajiasghar-Sharbaf; Hossein Asgarian-Omran; Reza Valadan; Hadi  Hossein-Nattaj; Ramin Shekarriz; Ehsan Zaboli; Ghasem Janbabaei; Mohsen Tehrani

doi:10.18502/ijaai.v20i6.8027

Reza Hajiasghar-Sharbaf Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Hossein Asgarian-Omran Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Reza Valadan Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Hadi Hossein-Nattaj Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Ramin Shekarriz Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Ehsan Zaboli Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Ghasem Janbabaei Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Mohsen Tehrani Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

DOI: https://doi.org/10.18502/ijaai.v20i6.8027

Keywords: Chronic lymphocytic leukemia; TIGIT protein

Abstract

The role of immune checkpoint receptors in T-cell exhaustion has been demonstrated in several cancers. We investigated the co-expression of TIGIT/PD-1 and LAG-3/PD-1 cells in patients with chronic lymphocytic leukemia (CLL).

The frequencies of TIGIT⁺PD-1⁺CD8⁺and LAG-3⁺PD-1⁺CD8⁺cells and relative mRNA expression of LSECtin and CD155 were examined in PBMCs from 33 CLL patients and 20 controls.

The percentage of TIGIT⁺PD-1⁺CD8⁺cells was significantly higher in CLL patients than in control subjects, with the preference in advanced-stage patients. However, LAG-3⁺PD-1⁺CD8⁺cell percentage was significantly lower in CLL patients than in the control subjects, and no significant differences were found between the early and advanced stages of the disease. An increase in the mRNA expression level of LSECtin, but not that of CD155, was observed in CLL patients compared to the control subjects.

Collectively, a higher co-expression of PD-1 and TIGIT on CD8⁺ T-cells in CLL compared to control subjects suggests an important role of TIGIT in T-cell exhaustion in CLL patients especially those with advanced disease.