Identification and characterization of the specific murine NK cell subset supporting graft-versus-leukemia- and reducing graft-versus-host-effects

被引：34

作者：

Meinhardt, Kathrin ^{[1
,2
,3
]}

Kroeger, Irena ^{[1
]}

Bauer, Ruth ^{[1
,2
,3
]}

Ganss, Franziska ^{[1
,2
,3
]}

Ovsiy, Ilja ^{[2
,3
]}

Rothamer, Johanna ^{[1
,2
,3
]}

Buettner, Maike ^{[4
]}

Atreya, Imke ^{[5
]}

Waldner, Maximilian ^{[5
]}

Bittrich, Max ^{[1
]}

Lehmann, Christian H. K. ^{[6
]}

Rieger, Michael A. ^{[3
,7
]}

Beilhack, Andreas ^{[8
]}

Zeiser, Robert ^{[9
]}

Edinger, Matthias ^{[10
,11
]}

Dudziak, Diana ^{[6
]}

Mackensen, Andreas ^{[1
]}

Rehli, Michael ^{[10
,11
]}

Ullrich, Evelyn ^{[1
,2
,3
]}

机构：

[1] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Internal Med Hematol & Oncol 5, D-91054 Erlangen, Germany

[2] Goethe Univ Frankfurt, Childrens Hosp, Dept Pediat Hematol & Oncol, D-60054 Frankfurt, Germany

[3] Goethe Univ Frankfurt, LOEWE Ctr Cell & Gene Therapy, D-60054 Frankfurt, Germany

[4] Univ Erlangen Nurnberg, Dept Nephropathol, Univ Hosp Erlangen, D-91054 Erlangen, Germany

[5] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Internal Med 1, D-91054 Erlangen, Germany

[6] Univ Erlangen Nurnberg, Dept Dermatol, Univ Hosp Erlangen, Lab Dendrit Cell Biol, D-91054 Erlangen, Germany

[7] Goethe Univ Frankfurt, Dept Hematol Oncol, D-60054 Frankfurt, Germany

[8] Univ Hosp, IZKF Res Grp Expt Stem Cell Transplantat, Dept Med 2, Wurzburg, Germany

[9] Univ Freiburg, Div Hematol & Oncol, Dept Med, Freiburg Univ Med Ctr, D-79106 Freiburg, Germany

[10] Univ Hosp Regensburg, Dept Internal Med 3, Regensburg, Germany

[11] Univ Regensburg, Regensburg Ctr Intervent Immunol RCI, D-93053 Regensburg, Germany

来源：

ONCOIMMUNOLOGY | 2015年 / 4卷 / 01期

关键词：

GVHD; GVL; NK cells; stem cell transplantation; tumor immunology; NATURAL-KILLER-CELLS; BONE-MARROW-TRANSPLANTATION; KIR LIGAND INCOMPATIBILITY; ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC TRANSPLANTS; PHASE-II; T-CELLS; EXPANSION; CANCER; IMMUNOTHERAPY;

D O I：

10.4161/2162402X.2014.981483

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Clinical studies investigating the impact of natural killer (NK) cells in allogeneic hematopoietic stem cell transplantation settings have yielded promising results. However, NK cells are a functionally and phenotypically heterogeneous population. Therefore, we addressed the functional relevance of specific NK cell subsets distinguished by expression of CD117, CD27 and CD11b surface markers in graft-versus-leukemia (GVL)-reaction and graft-versus-host-disease (GVHD). Our results clearly demonstrate that the subset of c-Kit(-)CD27(-)CD11b(+) NK cells expressed multiple cytotoxic pathway genes and provided optimal graft-versus-leukemia-effects, while significantly reducing T cell proliferation induced by allogeneic dendritic cells. Furthermore, these NK cells migrated to inflamed intestinal tissues where graft-versus-host-colitis was efficiently mitigated. For the first time, we identified the c-Kit(-)CD27(-)CD11b(+) NK cell population as the specific effector NK cell subset capable of significantly diminishing GVHD in fully mismatched bone marrow transplantation settings. In conclusion, the subset of c-Kit(-)CD27(-)CD11b(+) NK cells not only supports GVL, but also plays a unique role in the protection against GVHD by migrating to the peripheral GVHD target organs where they exert efficient immunoregulatory activities. These new insights demonstrate the importance of selecting the optimal NK cell subset for cellular immunotherapy following allogeneic hematopoietic stem cell transplantation.

引用

页数：12

共 35 条

[1] Suppression of graft-versus-host disease and amplification of graft-versus-tumor effects by activated natural killer cells after allogeneic bone marrow transplantation [J].