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

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2015 Dec 5

PMID 26635797

Citations 13

Authors

Benedikt Jacobs

Sara Tognarelli

Kerstin Poller

Peter Bader

Andreas Mackensen

Evelyn Ullrich

Affiliations

Soon will be listed here.

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.

Citing Articles

Day 100 Recovery of Absolute Number of Inhibitory KIR2DL2 and Activating NKp30 Natural Killer Cells Predicts Survival Post-Autologous Stem Cell Transplantation in Lymphomas.

Porrata L, Ansell S, Micallef I, Johnston P, Villasboas J, Paludo J Biomedicines. 2024; 12(8).

PMID: 39200272 PMC: 11351217. DOI: 10.3390/biomedicines12081808.

Natural killer cells affect the natural course, drug resistance, and prognosis of multiple myeloma.

Zhang L, Peng X, Ma T, Liu J, Yi Z, Bai J Front Cell Dev Biol. 2024; 12:1359084.

PMID: 38410372 PMC: 10895066. DOI: 10.3389/fcell.2024.1359084.

Natural Killer Cells Are Key Host Immune Effector Cells Affecting Survival in Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation.

Porrata L Cells. 2022; 11(21).

PMID: 36359863 PMC: 9657161. DOI: 10.3390/cells11213469.

expansion of a CD9 decidual-like NK cell subset following autologous hematopoietic stem cell transplantation.

Orrantia A, Vazquez-De Luis E, Astarloa-Pando G, Terren I, Amarilla-Irusta A, Polanco-Alonso D iScience. 2022; 25(10):105235.

PMID: 36262311 PMC: 9574507. DOI: 10.1016/j.isci.2022.105235.

The Impact of Infused Autograft Absolute Numbers of Immune Effector Cells on Survival Post-Autologous Stem Cell Transplantation.

Porrata L Cells. 2022; 11(14).

PMID: 35883639 PMC: 9315986. DOI: 10.3390/cells11142197.

References

Perales M, Ceberio I, Armand P, Burns L, Chen R, Cole P . Role of cytotoxic therapy with hematopoietic cell transplantation in the treatment of Hodgkin lymphoma: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015; 21(6):971-83. DOI: 10.1016/j.bbmt.2015.02.022. View

Dulphy N, Haas P, Busson M, Belhadj S, Peffault de Latour R, Robin M . An unusual CD56(bright) CD16(low) NK cell subset dominates the early posttransplant period following HLA-matched hematopoietic stem cell transplantation. J Immunol. 2008; 181(3):2227-37. DOI: 10.4049/jimmunol.181.3.2227. View

Rueff J, Medinger M, Heim D, Passweg J, Stern M . Lymphocyte subset recovery and outcome after autologous hematopoietic stem cell transplantation for plasma cell myeloma. Biol Blood Marrow Transplant. 2014; 20(6):896-9. DOI: 10.1016/j.bbmt.2014.03.007. View

Bjorkstrom N, Riese P, Heuts F, Andersson S, Fauriat C, Ivarsson M . Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell differentiation uncoupled from NK-cell education. Blood. 2010; 116(19):3853-64. DOI: 10.1182/blood-2010-04-281675. View

Czaja K, Borer A, Schmied L, Terszowski G, Stern M, Gonzalez A . A comprehensive analysis of the binding of anti-KIR antibodies to activating KIRs. Genes Immun. 2013; 15(1):33-7. DOI: 10.1038/gene.2013.58. View

Ullrich E, Koch J, Cerwenka A, Steinle A . New prospects on the NKG2D/NKG2DL system for oncology. Oncoimmunology. 2013; 2(10):e26097. PMC: 3862635. DOI: 10.4161/onci.26097. View

Foley B, Cooley S, Verneris M, Curtsinger J, Luo X, Waller E . NK cell education after allogeneic transplantation: dissociation between recovery of cytokine-producing and cytotoxic functions. Blood. 2011; 118(10):2784-92. PMC: 3172795. DOI: 10.1182/blood-2011-04-347070. View

Chen Y, Wang M, Romaguera J . Current regimens and novel agents for mantle cell lymphoma. Br J Haematol. 2014; 167(1):3-18. DOI: 10.1111/bjh.13000. View

Vukicevic M, Chalandon Y, Helg C, Matthes T, Dantin C, Huard B . CD56bright NK cells after hematopoietic stem cell transplantation are activated mature NK cells that expand in patients with low numbers of T cells. Eur J Immunol. 2010; 40(11):3246-54. DOI: 10.1002/eji.200940016. View

10.

Boyiadzis M, Memon S, Carson J, Allen K, Szczepanski M, Vance B . Up-regulation of NK cell activating receptors following allogeneic hematopoietic stem cell transplantation under a lymphodepleting reduced intensity regimen is associated with elevated IL-15 levels. Biol Blood Marrow Transplant. 2008; 14(3):290-300. DOI: 10.1016/j.bbmt.2007.12.490. View

11.

Peruzzi G, Femnou L, Gil-Krzewska A, Borrego F, Weck J, Krzewski K . Membrane-type 6 matrix metalloproteinase regulates the activation-induced downmodulation of CD16 in human primary NK cells. J Immunol. 2013; 191(4):1883-94. PMC: 3745217. DOI: 10.4049/jimmunol.1300313. View

12.

Bosch M, Dhadda M, Hoegh-Petersen M, Liu Y, Hagel L, Podgorny P . Immune reconstitution after anti-thymocyte globulin-conditioned hematopoietic cell transplantation. Cytotherapy. 2012; 14(10):1258-75. PMC: 3681879. DOI: 10.3109/14653249.2012.715243. View

13.

Porrata L, Inwards D, Micallef I, Johnston P, Ansell S, Hogan W . Interleukin-15 affects patient survival through natural killer cell recovery after autologous hematopoietic stem cell transplantation for non-Hodgkin lymphomas. Clin Dev Immunol. 2010; 2010:914945. PMC: 2855983. DOI: 10.1155/2010/914945. View

14.

Loza M, Perussia B . The IL-12 signature: NK cell terminal CD56+high stage and effector functions. J Immunol. 2003; 172(1):88-96. DOI: 10.4049/jimmunol.172.1.88. View

15.

Ljunggren H, Karre K . Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism. J Exp Med. 1985; 162(6):1745-59. PMC: 2187973. DOI: 10.1084/jem.162.6.1745. View

16.

Porrata L, Litzow M, Tefferi A, Letendre L, Kumar S, Geyer S . Early lymphocyte recovery is a predictive factor for prolonged survival after autologous hematopoietic stem cell transplantation for acute myelogenous leukemia. Leukemia. 2002; 16(7):1311-8. DOI: 10.1038/sj.leu.2402503. View

17.

Fischer J, Ottinger H, Ferencik S, Sribar M, Punzel M, Beelen D . Relevance of C1 and C2 epitopes for hemopoietic stem cell transplantation: role for sequential acquisition of HLA-C-specific inhibitory killer Ig-like receptor. J Immunol. 2007; 178(6):3918-23. DOI: 10.4049/jimmunol.178.6.3918. View

18.

Hamann I, Unterwalder N, Cardona A, Meisel C, Zipp F, Ransohoff R . Analyses of phenotypic and functional characteristics of CX3CR1-expressing natural killer cells. Immunology. 2011; 133(1):62-73. PMC: 3088968. DOI: 10.1111/j.1365-2567.2011.03409.x. View

19.

Pical-Izard C, Crocchiolo R, Granjeaud S, Kochbati E, Just-Landi S, Chabannon C . Reconstitution of natural killer cells in HLA-matched HSCT after reduced-intensity conditioning: impact on clinical outcome. Biol Blood Marrow Transplant. 2015; 21(3):429-39. DOI: 10.1016/j.bbmt.2014.11.681. View

20.

Shah N, Callander N, Ganguly S, Gul Z, Hamadani M, Costa L . Hematopoietic Stem Cell Transplantation for Multiple Myeloma: Guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015; 21(7):1155-66. DOI: 10.1016/j.bbmt.2015.03.002. View