Leila Hadadi1, Morteza Hafezi2, Ali Akbar Amirzargar3, Ramazan Ali Sharifian4, Saeid Abediankenari1,5, Hossein Asgarian-Omran6,7. 1. Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. 2. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. 3. Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 4. Clinic of Hematology and Oncology, Vali-Asr Hospital, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 5. Immunogenetics Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. 6. Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran, asgarianhossein@yahoo.com. 7. Immunogenetics Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran, asgarianhossein@yahoo.com.
Abstract
BACKGROUND: In this study, the expression pattern of NKp30 and T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3), as candidates for activating and inhibitory receptors of NK cells, were evaluated in patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: 24 CLL patients and 19 healthy controls were enrolled. Fresh peripheral blood was collected from all subjects and stained with fluorochrome-conjugated antibodies. The frequency of CD56+/CD3-/NKp30+ and CD56+/CD3-/Tim-3+ cells was determined by multicolor flow cytometry. RESULTS: Our results revealed that Tim-3 is significantly upregulated on natural killer (NK) cells of CLL patients in comparison to healthy controls. NK cells of CLL patients showed lower expression of NKp30-activating receptor compared to controls. Tim-3 expression pattern on NK cells of CLL patients was correlated with poor prognostic factors including low hemoglobin level, high absolute lymphocyte count, and high serum C-reactive protein level. CONCLUSION: Dysregulated expression of Tim-3 and NKp30 receptors confirms the exhaustion state of NK cells in CLL. Our data introduce Tim-3 as a promising biomarker and potential target for immunotherapy of CLL.
BACKGROUND: In this study, the expression pattern of NKp30 and T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3), as candidates for activating and inhibitory receptors of NK cells, were evaluated in patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: 24 CLL patients and 19 healthy controls were enrolled. Fresh peripheral blood was collected from all subjects and stained with fluorochrome-conjugated antibodies. The frequency of CD56+/CD3-/NKp30+ and CD56+/CD3-/Tim-3+ cells was determined by multicolor flow cytometry. RESULTS: Our results revealed that Tim-3 is significantly upregulated on natural killer (NK) cells of CLL patients in comparison to healthy controls. NK cells of CLL patients showed lower expression of NKp30-activating receptor compared to controls. Tim-3 expression pattern on NK cells of CLL patients was correlated with poor prognostic factors including low hemoglobin level, high absolute lymphocyte count, and high serum C-reactive protein level. CONCLUSION: Dysregulated expression of Tim-3 and NKp30 receptors confirms the exhaustion state of NK cells in CLL. Our data introduce Tim-3 as a promising biomarker and potential target for immunotherapy of CLL.
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