Human allo-reactive CD4+T cells as strong mediators of anti-tumor immunity in NOD/scid mice engrafted with human acute lymphoblastic leukemia

被引:26
作者
Stevanovic, S. [1 ]
Griffioen, M. [1 ]
Nijmeijer, B. A. [2 ]
van Schie, M. L. J. [1 ]
Stumpf, A. N. [1 ]
Rutten, C. E. [1 ]
Willemze, R. [1 ]
Falkenburg, J. H. F. [1 ]
机构
[1] Leiden Univ, Med Ctr, Dept Hematol, NL-2300 RC Leiden, Netherlands
[2] Amsterdam Mol Therapeut, Amsterdam, Netherlands
关键词
CD4+T cells; Graft-versus-Leukemia effect; donor lymphocyte infusion; immunotherapy; allogeneic stem cell transplantation; BONE-MARROW-TRANSPLANTATION; DONOR LYMPHOCYTE INFUSION; VERSUS-HOST-DISEASE; CHRONIC MYELOID-LEUKEMIA; HLA CLASS-I; T-CELLS; DENDRITIC CELLS; LEUKOCYTE INFUSIONS; GENERATION; DEPLETION;
D O I
10.1038/leu.2011.222
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Adoptive immunotherapy with donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation (alloSCT) may not only mediate Graft-versus-Leukemia (GvL) reactivity, but also induce Graft-versus-Host Disease (GvHD). As HLA-class II molecules are predominantly expressed on hematopoietic cells, CD4+ T cells may selectively mediate GvL reactivity without GvHD. Here, we assessed the capacity of human CD4+ T cells to act as sole mediators of GvL reactivity in a NOD/scid mouse model for human acute lymphoblastic leukemia and chronic myeloid leukemia in lymphoid blast crisis. Highly purified CD4+ DLI eradicated the leukemic cells. The anti-tumor immunity was mediated by a polyclonal CD4+ T cell response comprising cytokine-producing T-helper and cytolytic T-effector cells directed against the mismatched HLA-class II molecules of the patients. Furthermore, primary leukemic cells acquired an antigen-presenting cell (APC) phenotype in vivo after DLI, as well as in vitro after co-culture with leukemia-specific CD4+ T cells. In conclusion, our results show that CD4+ T cells can be strong mediators of anti-tumor immunity, and provide evidence that cross-talk between CD4+ T cells and leukemic cells is the basis for induction of leukemic cells with an APC phenotype. These data emphasize the clinical relevance of CD4+ T cell based immunotherapy as treatment modality for hematological malignancies after alloSCT. Leukemia (2012) 26, 312-322; doi:10.1038/leu.2011.222; published online 23 August 2011
引用
收藏
页码:312 / 322
页数:11
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