Combined Blockade Of PD-1 and TIGIT is not Sufficient to Improve the Function Of CD8+ T-Cells in Chronic Lymphocytic Leukemia

Hatefi, Fatemeh; Asgarian-Omran, Hossein; Hossein-Nataj, Hadi; Akbar, Armin; Shekarriz, Ramin; Zaboli, Ehsan; Janbabai, Ghasem; Tehrani, Mohsen

doi:10.31557/APJCP.2022.23.7.2225

Combined Blockade Of PD-1 and TIGIT is not Sufficient to Improve the Function Of CD8+ T-Cells in Chronic Lymphocytic Leukemia

Document Type : Research Articles

Authors

¹ Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

² Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

³ Department of Hematology and Oncology, Imam Khomeini hospital, Mazandaran university of Medical sciences, Sari, Iran.

10.31557/APJCP.2022.23.7.2225

Abstract

Background and Objective: Blockade of immune checkpoint receptors in the treatment of cancers has been mentioned in several studies. Here, we investigated the efficacy of combined blockade of two inhibitory receptors, PD-1 and TIGIT, in restoring functional features of CD8+ T-cells in CLL. Methods: CD8+ T-cells were separated from the peripheral blood of 11 CLL patients and targeted with malignant B-cells isolated from the same patients. Cells were then stimulated with anti-CD3/CD28 and PMA/ionomycin to assess their proliferative response and cytotoxic activity using MTT and CD107a degranulation assays, respectively. Cytokine production of isolated CD8+ T-cells was also determined using ELISA. Results: There were no significant differences in proliferation and cytotoxic activity of CD8+ T-cells co-blocked with anti-PD-1/TIGIT compared to those single blocked with anti-PD-1, anti-TIGIT, or the control antibody. There was no significant difference in cytokine production of mentioned groups, either. Conclusions: Collectively, combined blockade of PD-1 and TIGIT failed to restore the proliferation and function of CD8+ T-cells isolated from CLL patients.

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