NK Cells in Chronic Lymphocytic Leukemia and Their Therapeutic Implications.
Biomarkers
Cell Communication
Disease Management
Disease Susceptibility
Humans
Immune System
/ immunology
Immunotherapy
/ adverse effects
Killer Cells, Natural
/ immunology
Leukemia, Lymphocytic, Chronic, B-Cell
/ diagnosis
Ligands
Protein Binding
Receptors, Natural Killer Cell
/ genetics
Treatment Outcome
Tumor Escape
/ genetics
CLL immune evasion
NK cell alterations
NK cell receptors
NK cell-based immunotherapy
NK cells
chronic lymphocytic leukemia
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
22 Jun 2021
22 Jun 2021
Historique:
received:
14
05
2021
revised:
16
06
2021
accepted:
18
06
2021
entrez:
2
7
2021
pubmed:
3
7
2021
medline:
24
7
2021
Statut:
epublish
Résumé
Key features of chronic lymphocytic leukemia (CLL) are defects in the immune system and the ability of leukemic cells to evade immune defenses and induce immunosuppression, resulting in increased susceptibility to infections and disease progression. Several immune effectors are impaired in CLL, including T and natural killer (NK) cells. The role of T cells in defense against CLL and in CLL progression and immunotherapy has been extensively studied. Less is known about the role of NK cells in this leukemia, and data on NK cell alterations in CLL are contrasting. Besides studies showing that NK cells have intrinsic defects in CLL, there is a large body of evidence indicating that NK cell dysfunctions in CLL mainly depend on the escape mechanisms employed by leukemic cells. In keeping, it has been shown that NK cell functions, including antibody-dependent cellular cytotoxicity (ADCC), can be retained and/or restored after adequate stimulation. Therefore, due to their preserved ADCC function and the reversibility of CLL-related dysfunctions, NK cells are an attractive source for novel immunotherapeutic strategies in this disease, including chimeric antigen receptor (CAR) therapy. Recently, satisfying clinical responses have been obtained in CLL patients using cord blood-derived CAR-NK cells, opening new possibilities for further exploring NK cells in the immunotherapy of CLL. However, notwithstanding the promising results of this clinical trial, more evidence is needed to fully understand whether and in which CLL cases NK cell-based immunotherapy may represent a valid, alternative/additional therapeutic option for this leukemia. In this review, we provide an overview of the current knowledge about phenotypic and functional alterations of NK cells in CLL and the mechanisms by which CLL cells circumvent NK cell-mediated immunosurveillance. Additionally, we discuss the potential relevance of using NK cells in CLL immunotherapy.
Identifiants
pubmed: 34206399
pii: ijms22136665
doi: 10.3390/ijms22136665
pmc: PMC8268440
pii:
doi:
Substances chimiques
Biomarkers
0
Ligands
0
Receptors, Natural Killer Cell
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : IG 2018 - ID 21352
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