TY - JOUR
T1 - At the Bench
T2 - Preclinical rationale for exploiting NK cells and γδ T lymphocytes for the treatment of high-risk leukemias
AU - Norell, Håkan
AU - Moretta, Alessandro
AU - Silva-Santos, Bruno
AU - Moretta, Lorenzo
PY - 2013/12
Y1 - 2013/12
N2 - NK cells and γδ T lymphocytes display potent cytolytic activity against leukemias and CMV-infected cells and are thus, prosmising immune effector cells in the context of allo-HSCT. NK cells express HLA class I-specific inhibitory receptors and preferentially kill HLA class Ilow tumors or virus-infected cells. Killing occurs upon engagement of activating NKRs with ligands that are up-regulated on tumors and infected cells. A similar activating receptor/ligand interaction strategy is used by γδ T cells, which in addition, use their TCRs for recognition of phosphorylated antigens and still largely undefined ligands on tumor cells. In the haploidentical allo-HSCT setting, alloreactive NK cells, derived from donor HSCs, can exert potent antileukemia activity and kill residual patient DCs and T cells, thus preventing GvHD and graft rejection. However, generation of KIR+ alloreactive NK cells from HSCs requires many weeks, during which leukemia relapses, and life-threatening infections may occur. Importantly, mature NK cells and γδ T cells can control certain infectious agents efficiently, in particular, limit CMV reactivation, and infusion of such donor cells at the time of HSCT has been implemented. Development of novel, cell-based immunotherapies, allowing improved trafficking and better targeting, will endow NK cells and γδ T lymphocytes with enhanced antitumor activity, also making them key reagents for therapies against solid tumors. The clinical aspects of using NK cells and γδ T lymphocytes against hematological malignancies, including the allo-HSCT context, are reviewed in the related side-by-side paper by Locatelli and colleagues [1].
AB - NK cells and γδ T lymphocytes display potent cytolytic activity against leukemias and CMV-infected cells and are thus, prosmising immune effector cells in the context of allo-HSCT. NK cells express HLA class I-specific inhibitory receptors and preferentially kill HLA class Ilow tumors or virus-infected cells. Killing occurs upon engagement of activating NKRs with ligands that are up-regulated on tumors and infected cells. A similar activating receptor/ligand interaction strategy is used by γδ T cells, which in addition, use their TCRs for recognition of phosphorylated antigens and still largely undefined ligands on tumor cells. In the haploidentical allo-HSCT setting, alloreactive NK cells, derived from donor HSCs, can exert potent antileukemia activity and kill residual patient DCs and T cells, thus preventing GvHD and graft rejection. However, generation of KIR+ alloreactive NK cells from HSCs requires many weeks, during which leukemia relapses, and life-threatening infections may occur. Importantly, mature NK cells and γδ T cells can control certain infectious agents efficiently, in particular, limit CMV reactivation, and infusion of such donor cells at the time of HSCT has been implemented. Development of novel, cell-based immunotherapies, allowing improved trafficking and better targeting, will endow NK cells and γδ T lymphocytes with enhanced antitumor activity, also making them key reagents for therapies against solid tumors. The clinical aspects of using NK cells and γδ T lymphocytes against hematological malignancies, including the allo-HSCT context, are reviewed in the related side-by-side paper by Locatelli and colleagues [1].
KW - Blood cancer
KW - Cytomegalovirus
KW - Haploidentical
KW - Hematopoietic stem cell transplantation
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U2 - 10.1189/jlb.0613312
DO - 10.1189/jlb.0613312
M3 - Article
C2 - 24108703
AN - SCOPUS:84888812471
VL - 94
SP - 1123
EP - 1139
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 6
ER -