期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 94, 期 6, 页码 1123-1139出版社
OXFORD UNIV PRESS
DOI: 10.1189/jlb.0613312
关键词
blood cancer; hematopoietic stem cell transplantation; haploidentical; cytomegalovirus
资金
- European Union [PCOFUND-GA-2009-246542]
- Fundacao para a Ciencia e Tecnologia of Portugal [EXPL/BIM-ONC/0490/2012]
- Associazione Italiana Ricerca sul Cancro (AIRC), IG [10225]
- Special Program Molecular Clinical Oncology 5 x 1000 Project [9962]
- MIUR: MIUR-FIRB [RBLA039LSF-001]
- MIUR-PRIN [2008PTB3HC_005]
- Ministero della Salute [2006-08]
- Fundação para a Ciência e a Tecnologia [EXPL/BIM-ONC/0490/2012] Funding Source: FCT
Basic Research Review for Clinicians: Mechanisms underlying the anti-tumor and anti-CMV functions of NK cells, and T cells, as the preclinical basis of high risk leukemia treatment, focusing on hematopoietic stem cell transplantation. NK cells and T lymphocytes display potent cytolytic activity against leukemias and CMV-infected cells and are thus, promising immune effector cells in the context of allo-HSCT. NK cells express HLA class I-specific inhibitory receptors and preferentially kill HLA class I-low 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 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 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 T lymphocytes with enhanced anti-tumor activity, also making them key reagents for therapies against solid tumors. The clinical aspects of using NK cells and T lymphocytes against hematological malignancies, including the allo-HSCT context, are reviewed in the related side-by-side paper by Locatelli and colleagues [1].
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