scholarly journals KIR Receptors as Key Regulators of NK Cells Activity in Health and Disease

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1777
Author(s):  
Joanna Dębska-Zielkowska ◽  
Grażyna Moszkowska ◽  
Maciej Zieliński ◽  
Hanna Zielińska ◽  
Anna Dukat-Mazurek ◽  
...  
Keyword(s):  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Nk Cell ◽  
Solid Organ Transplantation ◽  
Cell Activity ◽  
Solid Organ ◽  
Adoptive Therapy ◽  
Hematopoietic Stem ◽  
Kir Receptors

Natural killer (NK) cells are part of the cellular immune response. They target mainly cancer and virally infected cells. To a high extent cytotoxic activity of NK cells is regulated inter alia by signals from killer immunoglobulin-like receptors (KIR). The major histocompatibility complex (MHC) class I molecules are important ligands for KIR receptors. Binding of ligands (such as MHC I) to the KIR receptors has the important role in solid organ or hematopoietic cell transplantation. Of note, the understanding of the relationship between KIR and MHC receptors may contribute to the improvement of transplant results. Donor-recipient matching, which also includes the KIR typing, may improve monitoring, individualize the treatment and allow for predicting possible effects after transplantation, such as the graft-versus-leukemia effect (GvL) or viral re-infection. There are also less evident implications of KIR/MHC matching, such as with pregnancy and cancer. In this review, we present the most relevant literature reports on the importance of the KIR/MHC relationship on NK cell activity and hematopoietic stem cell transplantation (HSCT)/solid organ transplantation (SOT) effects, the risk of allograft rejection, protection against post-transplant cytomegalovirus (CMV) infection, pregnancy complications, cancer and adoptive therapy with NK cells.

scholarly journals Human NK Cells in Autologous Hematopoietic Stem Cell Transplantation for Cancer Treatment

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1589
Author(s):  
Ane Orrantia ◽  
Iñigo Terrén ◽  
Gabirel Astarloa-Pando ◽  
Olatz Zenarruzabeitia ◽  
Francisco Borrego
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cell Biology ◽  
Nk Cell ◽  
Hematopoietic Stem ◽  
Autologous Hsct

Natural killer (NK) cells are phenotypically and functionally diverse lymphocytes with the ability to recognize and kill malignant cells without prior sensitization, and therefore, they have a relevant role in tumor immunosurveillance. NK cells constitute the main lymphocyte subset in peripheral blood in the first week after hematopoietic stem cell transplantation (HSCT). Although the role that NK cells play in allogenic HSCT settings has been documented for years, their significance and beneficial effects associated with the outcome after autologous HSCT are less recognized. In this review, we have summarized fundamental aspects of NK cell biology, such as, NK cell subset diversity, their effector functions, and differentiation. Moreover, we have reviewed the factors that affect autologous HSCT outcome, with particular attention to the role played by NK cells and their receptor repertoire in this regard.

scholarly journals Donor and host coexpressing KIR ligands promote NK education after allogeneic hematopoietic stem cell transplantation

2019 ◽  
Vol 3 (24) ◽  
pp. 4312-4325 ◽  
Author(s):  
Xiang-Yu Zhao ◽  
Xing-Xing Yu ◽  
Zheng-Li Xu ◽  
Xun-Hong Cao ◽  
Ming-Rui Huo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Nk Cell ◽  
K562 Cells ◽  
Inhibitory Receptors ◽  
Hematopoietic Stem

Abstract The rate and extent of natural killer (NK)–cell education after hematopoietic cell transplantation correlates with leukemia control. To study the effect of donor and host HLA on NK-cell reconstitution, single killer-cell immunoglobulin-like receptor (KIR)+ NK cells (exhibiting KIR2DL1, KIR2DL2/KIR2DL3, or KIR3DL1 as their sole receptor) were grouped into 4 groups based on the interaction between donor/host HLA and donor inhibitory KIR in 2 cohorts (n = 114 and n = 276, respectively). On days 90 to 180 after transplantation, the absolute number and responsiveness against K562 cells (CD107a or interferon-γ expression) of single-KIR+ NK cells were higher in pairs where donor and host HLA both expressed ligands for donor inhibitory KIRs than in pairs where 1 or both of the donor and recipient HLA lacked at least 1 KIR ligand. NK-cell responsiveness was tuned commensurate with the number of inhibitory receptors from the donor. When both donor and host expressed the 3 major KIR ligands (HLA-C1, HLA-C2, and HLA-Bw4), NK cells expressing 3 inhibitory receptors (KIR2DL1/2DL3/3DL1) reached the maximum responsiveness against K562 cells compared with those NK cells expressing only 1 or 2 inhibitory receptors. When donor and host HLA both expressed all ligands for donor inhibitory KIRs, patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) showed the lowest recurrence rate after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). In conclusion, this study demonstrates that when both donors and hosts present all the KIR ligands for donor KIRs, reconstituted NK cells achieve better functional education and contribute to least relapse among patients. This observation study was registered at www.clinicaltrials.gov as #NCT02978274.

scholarly journals IL-2 and Anti-TGF-β Promote NK Cell Reconstitution and Anti-tumor Effects after Syngeneic Hematopoietic Stem Cell Transplantation

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3189 ◽  
Author(s):  
Maite Alvarez ◽  
Cordelia Dunai ◽  
Lam T. Khuat ◽  
Ethan G. Aguilar ◽  
Isabel Barao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Immune Cells ◽  
Nk Cell ◽  
Continuous Treatment ◽  
Hematopoietic Stem

The failure of autologous hematopoietic stem cell transplantation (HSCT) has been associated with a profound immunodeficiency that follows shortly after treatment, which renders patients susceptible to opportunistic infections and/or cancer relapse. Thus, given the additional immunosuppressive pathways involved in immune evasion in cancer, strategies that induce a faster reconstitution of key immune effector cells are needed. Natural killer (NK) cells mediate potent anti-tumor effector functions and are the first immune cells to repopulate after HSCT. TGF-β is a potent immunosuppressive cytokine that can impede both the development and function of immune cells. Here, we evaluated the use of an immunotherapeutic regimen that combines low dose of IL-2, an NK cell stimulatory signal, with TGF-β neutralization, in order to accelerate NK cell reconstitution following congenic HSCT in mice by providing stimulatory signals yet also abrogating inhibitory ones. This therapy led to a marked expansion of NK cells and accelerated NK cell maturation. Following HSCT, mature NK cells from the treated recipients displayed an activated phenotype and enhanced anti-tumor responses both in vitro and in vivo. No overt toxicities or adverse effects were observed in the treated recipients. However, these stimulatory effects on NK cell recovery were predicated upon continuous treatment as cessation of treatment led to return to baseline levels and to no improvement of overall immune recovery when assessed at later time-points, indicating strict regulatory control of the NK cell compartment. Overall, this study still demonstrates that therapies that combine positive and negative signals can be plausible strategies to accelerate NK cell reconstitution following HSCT and augment anti-tumor efficacy.

scholarly journals Mobilization with cyclophosphamide reduces the number of lymphocyte subpopulations in the leukapheresis product and delays their reconstitution after autologous hematopoietic stem cell transplantation in patients with multiple myeloma

2016 ◽  
Vol 50 (4) ◽  
pp. 402-408 ◽  
Author(s):  
Matevz Skerget ◽  
Barbara Skopec ◽  
Darja Zontar ◽  
Peter Cernelc
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
T Regulatory Cells ◽  
Nk Cell ◽  
Hematopoietic Stem ◽  
Cell Counts

Abstract Background Autologous hematopoietic stem cell transplantation is considered the standard of care for younger patients with multiple myeloma. Several mobilization regimens are currently used, most commonly growth factors alone or in combination with chemotherapy. The aim of our study was to investigate the differences in lymphocyte subpopulation counts between three different mobilization regimens on collection day, in the leukapheresis product and on day 15 after autologous hematopoietic stem cell transplantation. Patients and methods In total 48 patients were prospectively enrolled in three different mobilization regimens; (i) filgrastim (20), (ii) pegfilgrastim (19) and (iii) cyclophosphamide + filgrastim (9). Lymphocytes, CD16+/56+ natural killer and CD4+/CD25high T regulatory cells were determined by flow cytometry. Results We found a statistically significant difference between the mobilization regimens. Cyclophosphamide reduced lymphocyte and natural killer (NK) cell counts on collection day (lymphocytes 1.08 × 109/L; NK cells 0.07 × 109/L) compared to filgrastim (lymphocytes 3.08 × 109/L; NK cells 0.52 × 109/L) and pegfilgrastim (lymphocytes 3 × 109/L; NK cells 0.42 × 109/L). As a consequence lymphocyte and NK cell counts were also lower in the leukapheresis products following cyclophosphamide mobilization regimen (lymphocytes 50.1 × 109/L; NK cells 4.18 × 109/L) compared to filgrastim (lymphocytes 112 × 109/L; NK cells 17.5 × 109/L) and pegfilgrastim (lymphocytes 112 × 109/L; NK cells 14.3 × 109/L). In all mobilization regimens T regulatory cells increased 2-fold on collection day, regarding the base line value before mobilization. There was no difference in T regulatory cell counts between the regimens. Conclusions Mobilization with cyclophophamide reduces the number of mobilized and collected lymphocytes and NK cells as compared to mobilization with growth factors only and results in their delayed reconstitution following autologous hematopoietic stem cell transplantation. We found no difference between filgrastim and pegfilgrastim mobilization.

scholarly journals Dynamic Changes of Inhibitory Killer-Immunoglobulin-Like Receptors on NK Cells after Allogeneic Hematopoietic Stem Cell Transplantation: An Initial Study

2020 ◽  
Vol 9 (11) ◽  
pp. 3502
Author(s):  
Tereza Dekojová ◽  
Lucie Houdová ◽  
Jiří Fatka ◽  
Pavel Pitule ◽  
Pavel Ostašov ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Nk Cell ◽  
Ex Vivo ◽  
Post Transplantation ◽  
Hematopoietic Stem

Killer-immunoglobulin-like receptors (KIRs) are critical natural killer (NK) cell regulators. The expression of KIRs is a dynamic process influenced by many factors. Their ligands—HLA(Human Leukocyte Antigen) class I molecules—are expressed on all nucleated cells that keep NK cells under control. In hematopoietic stem cell transplantation (HSCT), NK cells play an essential role in relapse protection. In the presented pilot study, we characterized the dynamic expression of inhibitory KIRS (iKIRs), which protect cells against untoward lysis, in donors and patients during the first three months after HSCT using flow cytometry. The expression of all iKIRs was highly variable and sometimes correlated with patients’ clinical presentation and therapy regiment. Cyclophosphamide (Cy) in the graft-versus-host disease (GvHD) prevention protocol downregulated KIR2DL1 to just 25% of the original donor value, and the FEAM (Fludarabine + Etoposid + Ara-C + Melphalan) conditioning protocol reduced KIR2DL3. In lymphoid neoplasms, there was a slightly increased KIR2DL3 expression compared to myeloid malignancies. Additionally, we showed that the ex vivo activation of NK cells did not alter the level of iKIRs. Our study shows the influence of pre- and post-transplantation protocols on iKIR expression on the surface of NK cells and the importance of monitoring their cell surface.

The Unexpected and Differential Effect of Cyclosporin A on CD56Bright and CD56Dim NK Cell Expansion, Phenotype, Function and Development from Progenitor Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1404-1404
Author(s):  
Hongbo Wang ◽  
Alisa Lee ◽  
Valarie McCullar ◽  
Bruce R. Blazar ◽  
Jeffery S. Miller ◽  
...  
Keyword(s):  
Nk Cells ◽  
Progenitor Cells ◽  
Cell Transplantation ◽  
Cell Expansion ◽  
Hematopoietic Cell Transplantation ◽  
Nk Cell ◽  
Vehicle Control ◽  
Hematopoietic Cell ◽  
Receptor Expression ◽  
Ifn Γ

Abstract Following allogeneic hematopoietic cell transplantation, NK cells play important roles in hematopoietic cell engraftment, anti-viral responses, graft vs. host disease (GVHD) and graft vs. leukemia (GVL) reactions. Calcineurin inhibitors, such as cyclosporine A (CsA), are frequently administered to prevent or treat GVHD. It is generally considered that these immune suppressive agents inhibit GVL reactions. To date, little is known about the impact of these immune suppressants on NK cell function. To investigate this, NK cells were isolated from normal donors by negative selection and cultured with IL-2 (100 U/ml), IL-15 (10 ng/ml) and either physiological levels of CsA (1μg/ml) or vehicle control. Under these conditions, we consistently found that CsA treated cultures showed a reduction in NK cell expansion at one week (4.88 vs. 1.87 fold expansion, n=10). The phenotype of CsA treated NK cells was markedly different than controls. More specifically, after 7–10 days of culture with CsA there were significantly more CD56brightCD16− cells and significantly less CD56dimCD16+ cells compared to controls (p<0.001 for both). Accordingly, the percentage of KIR receptor (CD158a/h, CD158b/j and CD158e) expressing cells was significantly less in CsA treated cultures. No consistent changes were detected in the expression of NKG2D, NKp30, NKp44, or NKp46 on CsA treated NK cells relative to controls. To further investigate the influence of CsA on NK cell subset expansion, freshly isolated NK cells were stained with CFSE then cultured with CsA or vehicle control for 1 week. Using FACS we monitored CD56dimCD16+ and CD56brightCD16− cell division. There was no difference in the proliferation of CD56brightCD16− cells between the CsA and control treated cultures. In contrast, the CsA treated CD56dimCD16+ cells had fewer cell divisions, demonstrating that CsA selectively inhibits CD56dimCD16+ cell proliferation. These results were confirmed by determining the fold expansion of freshly isolated, FACS sorted CD56dimCD16+ and CD56brightCD16− populations cultured with CsA or vehicle control. To investigate the cytotoxicity of CsA treated NK cells, we performed killing assays using K562 and Raji cells as targets. Surprisingly, we consistently found higher cytotoxicity in CsA treated NK cells compared to controls (K562, p < 0.05 and Raji, p < 0.05). To further evaluate the functional activity of CsA treated NK cells, we investigated the intracellular IFN-γ secretion following IL-12/IL-18 stimulation. In 5 consecutive experiments the percentage of IFN-γ secreting cells was higher in CsA treated NK cells compared to vehicle controls (44% vs. 24%, p<0.05). Lastly, we determined the effect of CsA on NK cell differentiation from progenitor cells (CD34+Lin−CD38−) using an in vitro differentiation system. Briefly, progenitor cells were cultured on a murine feeder cell line (AFT-024) for 42 days in the presence of IL-3, IL-7, IL-15, SCF and FLT3L +/− CsA. We found that CsA treated cultures had less KIR expressing cells compared to controls. Collectively these results show that physiological levels of CsA inhibit CD56dimCD16+ cell growth and result in a population of NK cells that have less KIR receptor expression, higher cytotoxicity and more cytokine secretion. These findings may have important implications for both GVHD and GVL following hematopoietic cell transplantation.

Immune Reconstitution after Haploidentical Hematopoietic Cell Transplantation: Impact of Reduced Intensity Conditioning and CD3/CD19-Depleted Grafts

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1175-1175
Author(s):  
Birgit Federmann ◽  
Matthias Haegele ◽  
Christoph Faul ◽  
Wichard Vogel ◽  
Lothar Kanz ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Immune Reconstitution ◽  
Hematopoietic Cell Transplantation ◽  
Nk Cell ◽  
Reduced Intensity Conditioning ◽  
Haploidentical Hematopoietic Cell Transplantation ◽  
Reduced Intensity

Abstract Haploidentical hematopoietic cell transplantation (HHCT) using CD3/CD19 depleted grafts may lead to faster engraftment and immune reconstitution since grafts contain also graft-facilitating-cells, CD34− progenitors, NK cells, and dendritic cells. Reduced intensity conditioning may also have a positive impact on immune reconstitution following HHCT. 26 adults received CD3/CD19 depleted HHCT after RIC (150–200 mg/m2 fludarabine, 10mg/kg thiothepa, 120 mg/m2 melphalan and 5mg/day OKT-3 (day −5 to +14)) at our institution between 2005–2008. We prospectively evaluated engraftment and immune reconstitution. B-, NK-, T- and T-cell subsets (CD3/8, CD4/8, CD4/45RA/RO), TCR-Vβ repertoire and NK-cell receptors (NKP30, NKP44, NKP46, NKG2D, CD158a/b/e, CD85j, NKG2A, CD161) were analyzed by FACS. Grafts contained 8.8×106 CD34+ (range, 4.3–18.0 ×106), 2.9×104 CD3+ (range, 1.2–9.2×104) and 3.6×107 CD56+ (range, 0.02–23.0 ×107) cells/kg. Engraftment was rapid with a median time to &gt;500 granulocytes/μl of 11 days (range, 9–15) and a median time to &gt;20 000 platelets/μl of 11 days (range, 8–23). Full chimerism was reached on day 14 (median; range, 6–26). NK-cell engraftment was rapid, reaching normal values on day 20 (median of 247 CD16+CD56+CD3− cells/μl (range, 1–886)) with NK cells comprising up to 70% of lymphocytes. B-cell reconstitution was delayed with 81 (range, 0–280) and 335 (range, 11–452) CD19+20+ cells/μl on days 150 and 400, respectively. T-cell reconstitution was impaired with 49 (range, 0–586) and 364 (range, 35–536) CD3+ cells/μl on day 60 and day 150, respectively. We observed an increase of CD3+CD8+ cells in contrast to CD3+CD4+ cells early after HHCT with a median of 24 (range, 0–399) vs 16 (range, 0–257) and 159 (range, 1–402) vs 96 (range, 18–289) cells/μl on day 50 and day 200, respectively. CD4+CD45RA+ T cells increased slowly while CD4+CD45RO+ T cells reconstituted faster with a median of 61 CD4+CD45RO+ cells/μl (range, 0–310) vs 24 CD4+CD45RA+ (range, 0 to 152) on day 100. Within the CD4+CD25+ regulatory T cells there was a slow regeneration with median of 14 CD4+CD25+ cells/μl (range, 0–96) on day 100 and 28 CD4+CD25+ cells/μl (range, 19–160) on day 200. CD14+CD45+ monocytes did not reach normal values within the time of observation with 7 CD14+CD45+ cells/μl (range, 0–21) on day 120 and 7 CD14+CD45+ cells (range, 2–381) on day 400. TCR-Vβ repertoire and NK-cell receptor reconstitution was analyzed so far in 7 and 8 patients, respectively. We found a skewed T-cell repertoire with oligoclonal T-cell expansions to day 100 and normalization after day 200. An increased natural cytotoxicity receptor (NKP30, NKP44, NKP46) and NKG2A, but decreased NKG2D and KIR-expression was observed on NK-cells until day 100. In conclusion, T- and B-cell reconstitution is delayed after HHCT using CD3/CD19 depleted grafts and RIC. However, T-cell reconstitution is faster compared to data published with CD34 selected grafts and myeloablative conditioning. A fast NK-cell reconstitution early after HHCT was observed. Thus a combination of reduced intensity conditioning with CD3/CD19 depleted grafts appears to accelerate the immune recovery after haploidentical stem cell transplantation.

NK Cytotoxicity Is Decreased During the Early Posttransplant Period Following Pediatric Allogeneic Transplantation From Unrelated Donors Using CD3/CD19-Depleted Graft.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2434-2434
Author(s):  
Antonio Pérez-Martínez ◽  
Manuel Ramírez ◽  
María Ruiz-Salmerón ◽  
Marta Gonzalez-Vicent ◽  
S. Grande ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Nk Cell ◽  
Cell Subset ◽  
Median Number ◽  
Hematopoietic Stem ◽  
Unrelated Donors ◽  
Nk Cytotoxicity

Abstract Abstract 2434 Poster Board II-411 Introduction and objectives: Unrelated donors, match unrelated (MUD) and haploidentical donors (HSCT), have been described as a therapeutic option for high-risk childhood acute leukemia. CD3/CD19 depleted graft has been used in order to decrease the incidence of graft versus host disease (GvHD) and post-transplant lymphoproliferative disease, in the unrelated transplantation setting. Donor-derived NK cell alloreactivity has been reported to mediate early graft-versus-leukemia (GvL) effect after allogeneic hematopoietic stem cell transplantation. NK cells are components of the innate immunity playing an important role in the surveillance of human tumors. NK cell recognition of malignant cells depends on a dynamic balance between activating and inhibitory receptors. NK cell alloreactivity can be predicted by donor Killer Immunoglobulin like Receptors (KIRs), Natural Killer Receptors (NCRs), C-type Lectin receptors (NKG2D), Toll Like Receptors (TLRs) and recipient human leukocyte antigen (HLA) class I alleles as ligands. Reduced risk of relapsed has been described in malignant cancer after haploidentical stem cell transplantation when HLA ligands against the inhibitory KIRs present in the donor were absent in the recipient (KIR–HLA receptor–ligand mismatch). We prospectively investigated NK function and NK reconstitution in 18 CD3/CD19 depleted graft unrelated hematopoietic stem cell transplantation (7 MUD and 11 HSCT) using fludarabine-based reduced intensity conditioning regimen. Results: NK cells peaked around day 30 after transplantation. The median number of NK cells on day +30 was 403±88/μL . On day 100 after transplantation the median number of NK cells/μL was 221±58. While the CD56bright NK cell subset was above normal during the first 100 days post-transplant, the “effector” NK cell subset, CD56dim CD16bright, was significantly reduced early after transplantation. The median percentage of CD56bright cells among NK cells in peripheral blood was 25.8±4.6% at day +30, and it was 24.5±5.7 at day +100. The decreased in CD56dim CD16bright NK cell subset was correlated with the decreased of the inhibitory KIR receptors (KIR2DL1, KIR2DL2, KIR3DL1) expression. We also observed a lower expression than donors of the activating receptors NKG2D, TLR4 at day +30, NKp46, TLR 9 at day 60 and NKp46, NKp30 at day +100. Although absolute NK-cell counts rapidly increased after transplant, their cytotoxicity against K562 was much lower compared to that of their donors. At day 100 after transplantation, patients NK cytotoxicity was lower than donor values. These results suggest that the low NK cell cytotoxicity could be related to an “immature” NK phenotype during the early period after HSCT. As other authors have published, activating receptors can be significantly upregulated in cytokine-stimulated NK cells. In our experience, overnight incubation with IL-15 overcomes this limitation, enhancing three times NK cytotoxicity, in vitro. Conclusion: The phenotype of NK cells and NK cytotoxicity ability are significantly altered early after allogeneic transplantation from unrelated donors using CD3/CD19-depleted graft. NK repertoire observed in patients was associated with the imbalance between CD56bright and CD56dim NK subsets and the expression of KIRs and NCRs. These data suggest a pattern consistent with an ongoing NK maturation after MUD and HSCT transplantation. In our experience, the phenotype and functional pattern of NK cells observed is suggestive of a cytokine-driven process. IL-15 stimulated NK cells could be helpful to optimize adoptive antitumor NK immunotherapy to enhance GvL effect as early as possible after transplantation. Disclosures: No relevant conflicts of interest to declare.

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