Adaptive and Innate Cytotoxic Effectors in Chronic Lymphocytic Leukaemia (CLL) Subjects with Stable Disease
Chronic lymphocytic leukaemia (CLL) is characterised by the expansion of a neoplastic mature B cell clone. CLL clinical outcome is very heterogeneous, with some subjects never requiring therapy and some showing an aggressive disease. Genetic and epigenetic alterations and pro-inflammatory microenvir...
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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/11/9596 |
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| author | Valentina Rubino Flavia Carriero Anna Teresa Palatucci Angela Giovazzino Stefania Leone Valerio Nicolella Martina Calabrò Rosangela Montanaro Vincenzo Brancaleone Fabrizio Pane Federico Chiurazzi Giuseppina Ruggiero Giuseppe Terrazzano |
| author_facet | Valentina Rubino Flavia Carriero Anna Teresa Palatucci Angela Giovazzino Stefania Leone Valerio Nicolella Martina Calabrò Rosangela Montanaro Vincenzo Brancaleone Fabrizio Pane Federico Chiurazzi Giuseppina Ruggiero Giuseppe Terrazzano |
| author_sort | Valentina Rubino |
| collection | DOAJ |
| description | Chronic lymphocytic leukaemia (CLL) is characterised by the expansion of a neoplastic mature B cell clone. CLL clinical outcome is very heterogeneous, with some subjects never requiring therapy and some showing an aggressive disease. Genetic and epigenetic alterations and pro-inflammatory microenvironment influence CLL progression and prognosis. The involvement of immune-mediated mechanisms in CLL control needs to be investigated. We analyse the activation profile of innate and adaptive cytotoxic immune effectors in a cohort of 26 CLL patients with stable disease, as key elements for immune-mediated control of cancer progression. We observed an increase in CD54 expression and interferon (IFN)-γ production by cytotoxic T cells (CTL). CTL ability to recognise tumour-targets depends on human leukocyte antigens (HLA)-class I expression. We observed a decreased expression of HLA-A and HLA-BC on B cells of CLL subjects, associated with a significant reduction in intracellular calnexin that is relevant for HLA surface expression. Natural killer (NK) cells and CTL from CLL subjects show an increased expression of the activating receptor KIR2DS2 and a reduction of 3DL1 and NKG2A inhibiting molecules. Therefore, an activation profile characterises CTL and NK cells of CLL subjects with stable disease. This profile is conceivable with the functional involvement of cytotoxic effectors in CLL control. |
| first_indexed | 2024-03-11T03:05:05Z |
| format | Article |
| id | doaj.art-d974c2882a924ed5bf04cb9aca886736 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:05:05Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d974c2882a924ed5bf04cb9aca8867362023-11-18T08:01:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012411959610.3390/ijms24119596Adaptive and Innate Cytotoxic Effectors in Chronic Lymphocytic Leukaemia (CLL) Subjects with Stable DiseaseValentina Rubino0Flavia Carriero1Anna Teresa Palatucci2Angela Giovazzino3Stefania Leone4Valerio Nicolella5Martina Calabrò6Rosangela Montanaro7Vincenzo Brancaleone8Fabrizio Pane9Federico Chiurazzi10Giuseppina Ruggiero11Giuseppe Terrazzano12Department of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Science, University of Basilicata, 85100 Potenza, ItalyDepartment of Science, University of Basilicata, 85100 Potenza, ItalyDepartment of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, ItalyDivision of Hematology, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, ItalyDivision of Hematology, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Science, University of Basilicata, 85100 Potenza, ItalyDepartment of Science, University of Basilicata, 85100 Potenza, ItalyDivision of Hematology, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDivision of Hematology, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Science, University of Basilicata, 85100 Potenza, ItalyChronic lymphocytic leukaemia (CLL) is characterised by the expansion of a neoplastic mature B cell clone. CLL clinical outcome is very heterogeneous, with some subjects never requiring therapy and some showing an aggressive disease. Genetic and epigenetic alterations and pro-inflammatory microenvironment influence CLL progression and prognosis. The involvement of immune-mediated mechanisms in CLL control needs to be investigated. We analyse the activation profile of innate and adaptive cytotoxic immune effectors in a cohort of 26 CLL patients with stable disease, as key elements for immune-mediated control of cancer progression. We observed an increase in CD54 expression and interferon (IFN)-γ production by cytotoxic T cells (CTL). CTL ability to recognise tumour-targets depends on human leukocyte antigens (HLA)-class I expression. We observed a decreased expression of HLA-A and HLA-BC on B cells of CLL subjects, associated with a significant reduction in intracellular calnexin that is relevant for HLA surface expression. Natural killer (NK) cells and CTL from CLL subjects show an increased expression of the activating receptor KIR2DS2 and a reduction of 3DL1 and NKG2A inhibiting molecules. Therefore, an activation profile characterises CTL and NK cells of CLL subjects with stable disease. This profile is conceivable with the functional involvement of cytotoxic effectors in CLL control.https://www.mdpi.com/1422-0067/24/11/9596chronic lymphocytic leukaemiaHLA class I moleculescytotoxic T cellsNK cellsimmune activation profile |
| spellingShingle | Valentina Rubino Flavia Carriero Anna Teresa Palatucci Angela Giovazzino Stefania Leone Valerio Nicolella Martina Calabrò Rosangela Montanaro Vincenzo Brancaleone Fabrizio Pane Federico Chiurazzi Giuseppina Ruggiero Giuseppe Terrazzano Adaptive and Innate Cytotoxic Effectors in Chronic Lymphocytic Leukaemia (CLL) Subjects with Stable Disease International Journal of Molecular Sciences chronic lymphocytic leukaemia HLA class I molecules cytotoxic T cells NK cells immune activation profile |
| title | Adaptive and Innate Cytotoxic Effectors in Chronic Lymphocytic Leukaemia (CLL) Subjects with Stable Disease |
| title_full | Adaptive and Innate Cytotoxic Effectors in Chronic Lymphocytic Leukaemia (CLL) Subjects with Stable Disease |
| title_fullStr | Adaptive and Innate Cytotoxic Effectors in Chronic Lymphocytic Leukaemia (CLL) Subjects with Stable Disease |
| title_full_unstemmed | Adaptive and Innate Cytotoxic Effectors in Chronic Lymphocytic Leukaemia (CLL) Subjects with Stable Disease |
| title_short | Adaptive and Innate Cytotoxic Effectors in Chronic Lymphocytic Leukaemia (CLL) Subjects with Stable Disease |
| title_sort | adaptive and innate cytotoxic effectors in chronic lymphocytic leukaemia cll subjects with stable disease |
| topic | chronic lymphocytic leukaemia HLA class I molecules cytotoxic T cells NK cells immune activation profile |
| url | https://www.mdpi.com/1422-0067/24/11/9596 |
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