Combined Blockade Of PD-1 and TIGIT is not Sufficient to Improve the Function Of CD8+ T-Cells in Chronic Lymphocytic Leukemia |
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Authors: | Fatemeh HatefiHossein Asgarian-Omran Hadi Hossein-NatajArmin AkbarRamin Shekarriz Ehsan Zaboli Ghasem JanbabaiMohsen Tehrani |
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Institution: | 1Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.2Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran.3Department of Hematology and Oncology, Imam Khomeini hospital, Mazandaran university of Medical sciences, Sari, Iran. |
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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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Keywords: | Chronic Lymphocytic Leukemia PD-1 TIGIT T-cell exhaustion immune checkpoint blockade |
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