The More, The Better: "Do the Right Thing" For Natural Killer Immunotherapy in Acute Myeloid Leukemia.

Sarah Parisi,Antonio Curti,Michele Cavo,Marilena Ciciarello,Mariangela Lecciso,Giulia Corradi,Valentina Salvestrini,Darina Ocadlikova,Dorian Forte

doi:10.3389/fimmu.2017.01330

Sarah Parisi, Antonio Curti + Show 7 more

Open Access

https://doi.org/10.3389/fimmu.2017.01330

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Abstract

Natural killer (NK) cells are circulating CD3− lymphocytes, which express CD56 or CD16 and an array of inhibitory receptors, called killer-immunoglobulin-like receptors (KIRs). Alloreactive KIR-ligand mismatched NK cells crucially mediate the innate immune response and have a well-recognized antitumor activity. Adoptive immunotherapy with alloreactive NK cells determined promising clinical results in terms of response in acute myeloid leukemia (AML) patients and several data demonstrated that response can be influenced by the composition of NK graft. Several data show that there is a correlation between NK alloreactivity and clinical outcome: in a cohort of AML patients who received NK infusion with active disease, more alloreactive NK cell clones were found in the donor repertoire of responders than in non-responders. These findings demonstrate that the frequency of alloreactive NK cell clones influence clinical response in AML patients undergoing NK cell immunotherapy. In this work, we will review the most recent preclinical and clinical data about the impact of alloreactive NK cells features other than frequency of alloreactive clones and cytokine network status on their anti-leukemic activity. A better knowledge of these aspects is critical to maximize the effects of this therapy in AML patients.

Highlights

In the last years, major advances have been achieved in the understanding of acute myeloid leukemia (AML) biology [1]
In haploidentical stem cell transplantation (SCT), killer-immunoglobulin-like receptors (KIRs)-L mismatch dramatically impacts on the efficacy of Natural killer (NK) cells in enhancing anti-leukemia effect [15, 16, 23]. Whether these findings may be directly translated into the immunotherapy field has not been fully elucidated. In their pioneering study of adoptive NK immunotherapy, Miller et al showed that KIR-L mismatch between donor and recipient had a predictive value in terms of clinical response [20]
Our results indicate a highly predictive threshold of NK cells to be defined at the functional level (“functional dose”)

Summary

INTRODUCTION

Major advances have been achieved in the understanding of acute myeloid leukemia (AML) biology [1]. These preclinical results have weakly impacted on the clinical outcome of AML patients, whose prognosis is overall largely unsatisfactory [1,2,3,4]. For many patients, the cellular immunotherapy within SCT is hampered by the high risk of treatment-related morbidity and mortality. To expand the option of cellular immunotherapy besides the SCT setting, adoptive transfer of effector immune cells is a promising approach [5, 6]

NK Immunotherapy in AML

Host Regulatory T Cells

Findings

CONCLUSION