At the Bench: Preclinical rationale for exploiting NK cells and γδ T lymphocytes for the treatment of high-risk leukemias

Håkan Norell, Alessandro Moretta, Bruno Silva-Santos, Lorenzo Moretta

Research output: Contribution to journalArticle

Abstract

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].

Original languageEnglish
Pages (from-to)1123-1139
Number of pages17
JournalJournal of Leukocyte Biology
Volume94
Issue number6
DOIs
Publication statusPublished - Dec 2013

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Keywords

  • Blood cancer
  • Cytomegalovirus
  • Haploidentical
  • Hematopoietic stem cell transplantation

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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