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

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.

Enhancing the Activation and Releasing the Brakes: A Double Hit Strategy to Improve NK Cell Cytotoxicity Against Multiple Myeloma

“…This result was surprising as an NK cell activating effect of IMiDs and a more inhibitory effect of proteasome inhibitors have been previously reported (for review see ( 48 )). Furthermore, despite the differential expression of activating and inhibitory receptors in resting NK cells, especially the upregulation of NKG2A expression and the downregulation of CD57 expression at TP2, indicate a more immature NK cell phenotype, in line with earlier reports ( 28 ). In addition, lower TRAIL expression upon cytokine expression on NK cell from TP1 did not seem to have a negative influence on their anti-myeloma activity.…”

“…Furthermore, Sarkar and colleagues postulated that the most potent NK cell subset for clinical application would be NKG2A-negative and KIR-ligand mismatched. Interestingly, NKG2A is the first inhibitory receptor that is reconstituted after SCT ( 27 , 28 ). This observation might also highlight the possible relevance of NKG2A as a therapeutic target in the context of allogeneic SCT.…”

Variable Natural Killer Cell Activity in Hematological Malignancies at Diagnosis

“…Some studies highlighted the ability of NK cells to exert potent anti-leukemic effects and to reduce relapse in patients after autologous or allogeneic SCT [2,20,28,29]. In the present study, NKA of patients increased after SCT compared with that before SCT; these patients achieved complete remission.…”

Peripheral Immunotype Correlates with Minimal Residual Disease Status and Is Modulated by Immunomodulatory Drugs in Multiple Myeloma

“…Our data suggest a relative balance of cell surface receptors that deliver either inhibitory or activating signal on NK cells may be important in mediating MRD neg status. NK cell recovery both in number and function is quick after ASCT, generally within 1 month [14]. In our study MRD neg patients had more NK cells compared with MRD pos patients 2 months after ASCT.…”