Lack of cell movement impairs survival of peripheral blood IL-2-stimulated natural killer cells originating from solid cancer and promotes red blood cells to induce their switch toward a regulatory phenotype
Autor: | Zeyneb Hadjidj, Mourad Aribi, Rabia Messali |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Erythrocytes Cell Survival Immunology Cell Apoptosis Lymphocyte Activation 03 medical and health sciences 0302 clinical medicine Immune system Downregulation and upregulation Cell Movement Neoplasms medicine Humans Immunology and Allergy Extracellular Signal-Regulated MAP Kinases Cells Cultured Chemistry FOXP3 Cell Differentiation Phenotype Cell biology Killer Cells Natural 030104 developmental biology medicine.anatomical_structure Cell culture Cytokines Interleukin-2 Biomarkers Ex vivo Signal Transduction 030215 immunology |
Zdroj: | Immunology Letters. 221:6-17 |
ISSN: | 0165-2478 |
DOI: | 10.1016/j.imlet.2020.02.002 |
Popis: | Background Red blood cells (RBCs) can have a modulatory effect on immune cells; so changes in their dynamism could considerably influence their physiology, and consequently the immune activities of neighbouring cells, like natural killer (NK) cells. Herein, we studied the effect of both RBCs and lack of cell movement on the proliferation, survival and regulation of peripheral IL-2-stimulated NK cells from normal and solid malignant conditions. Methods Experiments were conducted on twelve cell culture groups, including NK cells from patients with solid malignant tumor or healthy controls, cultured alone or with autologous or nonautologous RBCs under shaking or no shaking conditions. Results NK cells from neoplastic patients behaved differently depending on the culture conditions including shaking and/or RBCs presence. Therefore, NK cells survival was downregulated in the absence of shaking; whereas, shaking have not only upregulated cell survival, but also downregulated the levels of p53-related apoptosis. Moreover, RBCs enhanced NK cells proliferation; while, this effect was modulated by shaking. Furthermore, RBCs can generate opposite effects on the production and modulation of protumoral or immunosuppressive cytokines, depending on the origin of NK cells, i.e., whether they derive from healthy or solid malignant tumor conditions. Finally, NK cells become able to express Foxp3 regulatory marker when combining three main conditions that include (i) treatment with high dose of IL-2, (ii) presence of RBCs, and (iii) absence of shaking. Conclusions Our outcomes showed for the first time that cell stagnation would be markedly involved in peripheral NK cell apoptosis, as well as in switching toward a regulatory phenotype-induced Foxp3. Cell movement may be one of ex vivo potential approaches in boosting the activities and survival of such cells during solid cancer. |
Databáze: | OpenAIRE |
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