Your browser doesn't support javascript.
loading
CLL-Derived Extracellular Vesicles Impair T-Cell Activation and Foster T-Cell Exhaustion via Multiple Immunological Checkpoints.
Böttcher, Martin; Böttcher-Loschinski, Romy; Kahlfuss, Sascha; Aigner, Michael; Gießl, Andreas; Mackensen, Andreas; Schlötzer-Schrehardt, Ursula; Tüting, Thomas; Bruns, Heiko; Mougiakakos, Dimitrios.
Afiliação
  • Böttcher M; Department of Hematology and Oncology, University Hospital Magdeburg, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany.
  • Böttcher-Loschinski R; Department of Hematology and Oncology, University Hospital Magdeburg, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany.
  • Kahlfuss S; Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany.
  • Aigner M; Health Campus Immunology, Infectiology, and Inflammation (GCI3), Medical Center, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany.
  • Gießl A; Institute of Medical Microbiology and Hospital Hygiene, Medical Faculty, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany.
  • Mackensen A; ChaMP, Center for Health and Medical Prevention, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany.
  • Schlötzer-Schrehardt U; Medical Department 5-Hematology and Oncology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
  • Tüting T; Department of Ophthalmology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
  • Bruns H; Medical Department 5-Hematology and Oncology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
  • Mougiakakos D; Department of Ophthalmology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
Cells ; 11(14)2022 07 12.
Article em En | MEDLINE | ID: mdl-35883619
Background: Chronic lymphocytic leukemia (CLL) is characterized by the clonal expansion of malignant B-cells and multiple immune defects. This leads, among others, to severe infectious complications and inefficient immune surveillance. T-cell deficiencies in CLL include enhanced immune(-metabolic) exhaustion, impaired activation and cytokine production, and immunological synapse malformation. Several studies have meanwhile reported CLL-cell-T-cell interactions that culminate in T-cell dysfunction. However, the complex entirety of their interplay is incompletely understood. Here, we focused on the impact of CLL cell-derived vesicles (EVs), which are known to exert immunoregulatory effects, on T-cell function. Methods: We characterized EVs secreted by CLL-cells and determined their influence on T-cells in terms of survival, activation, (metabolic) fitness, and function. Results: We found that CLL-EVs hamper T-cell viability, proliferation, activation, and metabolism while fostering their exhaustion and formation of regulatory T-cell subsets. A detailed analysis of the CLL-EV cargo revealed an abundance of immunological checkpoints (ICs) that could explain the detected T-cell dysregulations. Conclusions: The identification of a variety of ICs loaded on CLL-EVs may account for T-cell defects in CLL patients and could represent a barrier for immunotherapies such as IC blockade or adoptive T-cell transfer. Our findings could pave way for improving antitumor immunity by simultaneously targeting EV formation or multiple ICs.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Linfocítica Crônica de Células B / Vesículas Extracelulares Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cells Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Linfocítica Crônica de Células B / Vesículas Extracelulares Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cells Ano de publicação: 2022 Tipo de documento: Article