NK cell alloreactivity and allogeneic hematopoietic stem cell transplantation

Ruggeri, Loredana; Mancusi, Antonella; Burchielli, Emanuela; Capanni, Marusca; Carotti, Alessandra; Aloisi, Teresa; Aversa, Franco; Martelli, Massimo F.; Velardi, Andrea

doi:10.1016/j.bcmd.2007.06.029

Cited by 142 publications

(103 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The role of NK cells and their alloreactivity in allogeneic hematopoietic SCT (allo-HSCT) is currently controversial for different transplant settings. 1,[9][10][11][12][13][14] Our earlier study confirmed the deleterious role of a killer Ig-like receptor (KIR) ligand mismatch in this haploidentical GIAC protocol. 15,16 A further study also showed that the recovery of NK cells is, and can be used as, an indicator of the clinical outcome after unmanipulated haploidentical transplantation.…”

Section: Introductionsupporting

confidence: 53%

Association of natural killer cells in allografts with transplant outcomes in patients receiving G-CSF-mobilized PBSC grafts and G-CSF-primed BM grafts from HLA-haploidentical donors

et al. 2009

Bone Marrow Transplant

View full text Add to dashboard Cite

The aim of this study was to investigate the effects of natural killer (NK) cells on transplant outcomes in patients receiving G-CSF-mobilized PBSC grafts and G-CSF-primed BM grafts from HLA-haploidentical donors. Forty-one haploidentical allogeneic hematopoietic SCT patients were analyzed according to the NK cell concentration in relation to acute GVHD (aGVHD), chronic GVHD (cGVHD), TRM and leukemia-free survival. The patients receiving a higher dose of CD56 bright NK cells (41.9 Â 10 6 /kg) showed a higher incidence of grades II-IV aGVHD (hazard risk (HR), 2.872; P ¼ 0.022) and cGVHD (HR, 2.884; P ¼ 0.039). A higher CD56 dim /CD56 bri NK cell ratio (48.0) was correlated with a decreased risk of III-IV aGVHD (HR, 0.290; P ¼ 0.065) and TRM (HR, 0.072; P ¼ 0.012), thereby increasing the rate of leukemia-free survival (HR, 0.174; P ¼ 0.007) after haploidentical transplantation without in vitro T-cell depletion. Our results suggest that a high allograft CD56 dim /CD56 bright NK cell ratio (48.0) plays an important role in improving transplant outcomes. A higher dose of CD56 bright NK cells might be a predictor for a higher incidence of GVHD.

show abstract

Section: Introductionsupporting

confidence: 53%

Association of natural killer cells in allografts with transplant outcomes in patients receiving G-CSF-mobilized PBSC grafts and G-CSF-primed BM grafts from HLA-haploidentical donors

et al. 2009

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…33,34 Alloreactive NK cells reduced the risk of relapse of acute myeloid leukemia without increasing the incidence of GVHD, resulting in a marked improvement of event-free survival in a series of haploidentical transplant recipients. 35,36 In HLA-identical sibling transplants, the absence of HLA-C and HLA-B ligand for donor-inhibitory killer immunoglobulin-like receptors (KIR) provided benefits in terms of survival and relapse of patients with acute myeloid leukemia and myelodysplastic syndrome in recipients of T-cell-depleted SCT. 37 On the other hand, the JMDP found that KIR ligand mismatch was unfavorably correlated with relapse of leukemia and survival in patients undergoing T-cellreplete unrelated bone marrow transplants.…”

Section: Discussionmentioning

confidence: 99%

NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies

et al. 2009

View full text Add to dashboard Cite

BackgroundNKG2D, an activating and co-stimulatory receptor expressed on natural killer cells and T cells, plays pivotal roles in immunity to microbial infections as well as in cancer immunosurveillance. This study examined the impact of donor and recipient polymorphisms in the NKG2D gene on the clinical outcomes of patients undergoing allogeneic T-cell-replete myeloablative bone marrow transplantation using an HLA-matched unrelated donor. Design and MethodsThe NKG2D polymorphism was retrospectively analyzed in a total 145 recipients with hematologic malignancies and their unrelated donors. The patients underwent transplantation following myeloablative conditioning; the recipients and donors were matched through the Japan Marrow Donor Program. ResultsIn patients with standard-risk disease, the donor NKG2D-HNK1 haplotype, a haplotype expected to induce greater natural killer cell activity, was associated with significantly improved overall survival (adjusted hazard ratio, 0.44; 95% confidence interval, 0.23 to 0.85; p=0.01) as well as transplant related mortality (adjusted hazard ratio, 0.42; 95% confidence interval, 0.21 to 0.86; p=0.02), but had no impact on disease relapse or the development of grade II-IV acute graft-versus-host disease or chronic graft-versus-host disease. The NKG2D polymorphism did not significantly influence the transplant outcomes in patients with high-risk disease. ConclusionsThese data suggest an association between the donor HNK1 haplotype and better clinical outcome among recipients, with standard-risk disease, of bone marrow transplants from HLA-matched unrelated donors.

show abstract

“…172 The graft-vs.-tumor effect of alloreactive NK cells was also strengthened by mismatched IL-2-activated lymphocytes in patients with solid tumors or hematological malignancies. 173 As discussed above, autologous NK cells, allogeneic NK cells, NK cell lines and genetically modified NK cells were investigated for effectiveness as tumor immunotherapies.…”

Section: Clinical Trials Of Nk Cell-mediated Tumor Immunotherapymentioning

confidence: 99%

NK cell-based immunotherapy for malignant diseases

et al. 2013

View full text Add to dashboard Cite

Natural killer (NK) cells play critical roles in host immunity against cancer. In response, cancers develop mechanisms to escape NK cell attack or induce defective NK cells. Current NK cell-based cancer immunotherapy aims to overcome NK cell paralysis using several approaches. One approach uses expanded allogeneic NK cells, which are not inhibited by self histocompatibility antigens like autologous NK cells, for adoptive cellular immunotherapy. Another adoptive transfer approach uses stable allogeneic NK cell lines, which is more practical for quality control and large-scale production. A third approach is genetic modification of fresh NK cells or NK cell lines to highly express cytokines, Fc receptors and/or chimeric tumor-antigen receptors. Therapeutic NK cells can be derived from various sources, including peripheral or cord blood cells, stem cells or even induced pluripotent stem cells (iPSCs), and a variety of stimulators can be used for large-scale production in laboratories or good manufacturing practice (GMP) facilities, including soluble growth factors, immobilized molecules or antibodies, and other cellular activators. A list of NK cell therapies to treat several types of cancer in clinical trials is reviewed here. Several different approaches to NK-based immunotherapy, such as tissue-specific NK cells, killer receptor-oriented NK cells and chemically treated NK cells, are discussed. A few new techniques or strategies to monitor NK cell therapy by non-invasive imaging, predetermine the efficiency of NK cell therapy by in vivo experiments and evaluate NK cell therapy approaches in clinical trials are also introduced.

show abstract

NK cell alloreactivity and allogeneic hematopoietic stem cell transplantation

Cited by 142 publications

References 41 publications

Association of natural killer cells in allografts with transplant outcomes in patients receiving G-CSF-mobilized PBSC grafts and G-CSF-primed BM grafts from HLA-haploidentical donors

Association of natural killer cells in allografts with transplant outcomes in patients receiving G-CSF-mobilized PBSC grafts and G-CSF-primed BM grafts from HLA-haploidentical donors

NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies

NK cell-based immunotherapy for malignant diseases

Contact Info

Product

Resources

About