Multifunctional human CD56low CD16low natural killer cells are the prominent subset in bone marrow of both healthy pediatric donors and leukemic patients

Stabile, Helena; Nisti, Paolo; Morrone, Stefania; Pagliara, Daria; Bertaina, Alice; Locatelli, Franco; Santoni, Angela; Gismondi, Angela

doi:10.3324/haematol.2014.116053

Cited by 71 publications

(86 citation statements)

References 50 publications

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“…No significant difference in the CD56 dim CD16 dim NK subset was found between the chimeric and non-chimeric mice. However, the percentages of this population in bone marrow NK cells seemed to be higher than that recently reported for normal human bone marrow (28). Although there were no differences in any NK cell subsets in the peripheral blood of chimeric vs. non-chimeric mice, percentages of CD56 dim CD16 high and CD56 dim CD16 dim NK cells in human peripheral blood were significantly higher and lower, respectively, than those in the peripheral blood of both chimeric and non-chimeric mice.…”

Section: Resultscontrasting

confidence: 83%

Impact of Mixed Xenogeneic Porcine Hematopoietic Chimerism on Human NK Cell Recognition in a Humanized Mouse Model

Vishwasrao

Hölzl

et al. 2017

American Journal of Transplantation

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Mixed chimerism is a promising approach to inducing allograft and xenograft tolerance. Mixed allogeneic and xenogeneic chimerism in mouse models induced specific tolerance and global hyporesponsiveness, respectively, of host mouse NK cells. In this study, we investigated whether pig/human mixed chimerism could tolerize human NK cells in a humanized mouse model. Our results showed no impact of induced human NK cell reconstitution on porcine chimerism. NK cells from most pig/human mixed chimeric mice showed either specifically decreased cytotoxicity to pig cells or global hyporesponsiveness in an vitro cytotoxicity assay. Mixed xenogeneic chimerism did not hamper the maturation of human NK cells, but was associated with an alteration in NK cell subset distribution and IFN-γ production in the bone marrow. In summary, we demonstrate that mixed xenogeneic chimerism induces human NK cell hyporesponsiveness to pig cells. Our results support the use of this approach to inducing xenogeneic tolerance in the clinical setting. However, additional approaches are required to improve the efficacy of tolerance induction while assuring adequate NK cell functions.

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Section: Resultscontrasting

confidence: 83%

Impact of Mixed Xenogeneic Porcine Hematopoietic Chimerism on Human NK Cell Recognition in a Humanized Mouse Model

Vishwasrao

Hölzl

et al. 2017

American Journal of Transplantation

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“…In contrast, Mamessier et al (25) observed that the amount of circulating CD56 bright NK cells in BC patients increased in relation to the grade of malignancy. This result was also observed in the blood and bone marrow of pediatric leukemic patients in comparison with age-matched healthy controls (26). A major modulation in the proportion of circulating CD56 bright NK cells was described in the blood of melanoma patients compared with healthy donors: they were increased almost 3.6-fold within peripheral NK cells (from 12.2 6 6.3% to 43.5 6 17.5%) (27,28).…”

Section: Cd56supporting

confidence: 59%

Human CD56bright NK Cells: An Update

Michel

Poli

Cuapio

et al. 2016

The Journal of Immunology

326

273

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Human NK cells can be subdivided into various subsets based on the relative expression of CD16 and CD56. In particular, CD56brightCD16−/dim NK cells are the focus of interest. They are considered efficient cytokine producers endowed with immunoregulatory properties, but they can also become cytotoxic upon appropriate activation. These cells were shown to play a role in different disease states, such as cancer, autoimmunity, neuroinflammation, and infection. Although their phenotype and functional properties are well known and have been extensively studied, their lineage relationship with other NK cell subsets is not fully defined, nor is their precise hematopoietic origin. In this article, we summarize recent studies about CD56bright NK cells in health and disease and briefly discuss the current controversies surrounding them.

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“…Moreover, HNSCC patients had decreased numbers of peripheral cytotoxic CD56 dim /CD16 + NK cells and a shift toward CD56 bright NK cells. A bias toward CD56 bright NK cell subpopulation and reduced CD16 expression was also described for patients with advanced cancers, such as melanoma, breast cancer, esophageal squamous cell carcinoma, and pediatric leukemia (73–76). The reduction in CD16 + NK cell subsets is further correlated to decreased NK cell cytotoxicity and the immunosuppressive milieu of advanced cancers (73, 74, 77).…”

Section: Discussionmentioning

confidence: 81%

Natural Killer Group 2D Ligand Depletion Reconstitutes Natural Killer Cell Immunosurveillance of Head and Neck Squamous Cell Carcinoma

et al. 2017

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Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and aggressive tumor originating from the epithelial lining of the upper aero-digestive tract accounting for 300,000 annual deaths worldwide due to failure of current therapies. The natural killer group 2D (NKG2D) receptors on natural killer (NK) cells and several T cell subsets play an important role for immunosurveillance of HNSCC and are thus targeted by tumor immune evasion strategies in particular by shedding of various NKG2D ligands (NKG2DLs). Based on plasma and tumor samples of 44 HNSCC patients, we found that despite compositional heterogeneity the total plasma level of NKG2DLs correlates with NK cell inhibition and disease progression. Strikingly, based on tumor spheroids and primary tumors of HNSCC patients, we found that NK cells failed to infiltrate HNSCC tumors in the presence of high levels of NKG2DLs, demonstrating a novel mechanism of NKG2DL-dependent tumor immune escape. Therefore, the diagnostic acquisition of the plasma level of all NKG2DLs might be instrumental for prognosis and to decipher a patient cohort, which could benefit from restoration of NKG2D-dependent tumor immunosurveillance. Along these lines, we could show that removal of shed NKG2DLs (sNKG2DLs) from HNSCC patients’ plasma restored NK cell function in vitro and in individual patients following surgical removal of the primary tumor. In order to translate these findings into a therapeutic setting, we performed a proof-of-concept study to test the efficacy of adsorption apheresis of sNKG2DLs from plasma after infusion of human MICA in rhesus monkeys. Complete removal of MICA was achieved after three plasma volume exchanges. Therefore, we propose adsorption apheresis of sNKG2DLs as a future preconditioning strategy to improve the efficacy of autologous and adoptively transferred immune cells in cellular cancer immunotherapy.

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Multifunctional human CD56low CD16low natural killer cells are the prominent subset in bone marrow of both healthy pediatric donors and leukemic patients

Abstract: CD56high CD16+/-NK cells originate from CD34 + hematopoietic precursors through phenotypically distinct stages, whereas the CD56 low

Cited by 71 publications

References 50 publications

Impact of Mixed Xenogeneic Porcine Hematopoietic Chimerism on Human NK Cell Recognition in a Humanized Mouse Model

Impact of Mixed Xenogeneic Porcine Hematopoietic Chimerism on Human NK Cell Recognition in a Humanized Mouse Model

Human CD56bright NK Cells: An Update

Natural Killer Group 2D Ligand Depletion Reconstitutes Natural Killer Cell Immunosurveillance of Head and Neck Squamous Cell Carcinoma

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