NK Cell Subgroups, Phenotype, and Functions After Autologous Stem Cell Transplantation.

Benedikt Jacobs,Sara Tognarelli,Andreas Mackensen,Kerstin Poller,Peter Bader,Evelyn Ullrich

doi:10.3389/fimmu.2015.00583

Benedikt Jacobs, Sara Tognarelli + Show 4 more

Open Access

https://doi.org/10.3389/fimmu.2015.00583

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Abstract

High-dose chemotherapy with consecutive autologous stem cell transplantation (autoSCT) is a well-established treatment option for patients suffering from malignant lymphoma or multiple myeloma. Natural killer (NK) cells are an important part of the immune surveillance, and their cell number after autoSCT is predictive for progression-free and overall survival. To improve knowledge about the role of NK cells after autoSCT, we investigated different NK cell subgroups, their phenotype, and their functions in patients treated with autoSCT. Directly after leukocyte regeneration (>1000 leukocytes/μl) following autoSCT, CD56++ NK cells were the major NK cell subset. Surprisingly, these cells showed unusually high surface expression levels of CD57 and killer Ig-like receptors (KIRs) compared to expression levels before or at later time points after autoSCT. Moreover, these NK cells strongly upregulated KIR2DL2/3/S2 and KIR3DL1, whereas KIR2DL1/S1 remained constant, indicating that this cell population arose from more immature NK cells instead of from activated mature ones. Remarkably, NK cells were already able to degranulate and produce IFN-γ and MIP-1β upon tumor interaction early after leukocyte regeneration. In conclusion, we describe an unusual upregulation of CD57 and KIRs on CD56++ NK cells shortly after autoSCT. Importantly, these NK cells were functionally competent upon tumor interaction at this early time point.

Highlights

Natural killer (NK) cells are an important part of the innate immune system and are able to kill virus-infected or malignantly transformed cells [1]
Because there is no information available regarding the detailed analysis of NK cell subsets or function early after High-dose chemotherapy (HDC)/ autologous stem cell transplantation (autoSCT), in our study, we prospectively investigated the major NK cell subsets directly after leukocyte recovery and at later time points after HDC/autoSCT in patients with different lymphoproliferative diseases
In the setting of HDC/autoSCT, it has been demonstrated that a rapid NK cell recovery at 1 month after HDC/autoSCT is associated with a prolonged progression-free survival in MM [23] and non-Hodgkin lymphoma (NHL) patients [16]

Summary

Introduction

Natural killer (NK) cells are an important part of the innate immune system and are able to kill virus-infected or malignantly transformed cells [1]. Their important role in tumor surveillance has been demonstrated in many different tumor models [1]. NK cell cytotoxicity is regulated by a diverse repertoire of inhibitory and activating receptors. Inhibitory receptors, such as killer Ig-like receptors (KIRs) and the C-type lectin-like receptor NKG2A, recognize. NK Cells After Autologous SCT different alleles of HLA molecules (HLA-A, B, and C by KIRs and HLA-E by NKG2A) on healthy cells. Tumor cells may express stress-induced molecules, such as MHC I chain-related molecule A/B or UL-16-binding proteins, which are ligands for the activating NK cell receptor NKG2D [3, 4]

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