Tuning Natural Killer Cell Anti-multiple Myeloma Reactivity by Targeting Inhibitory Signaling via KIR and NKG2A

Niken M. Mahaweni; Femke A. I. Ehlers; Gerard M. J. Bos; Lotte Wieten

doi:10.3389/fimmu.2018.02848

Tuning Natural Killer Cell Anti-multiple Myeloma Reactivity by Targeting Inhibitory Signaling via KIR and NKG2A

Niken M. Mahaweni
, Femke A. I. Ehlers
, Gerard M. J. Bos
, Lotte Wieten^*

^*Corresponding author for this work

Research output: Contribution to journal › (Systematic) Review article › peer-review

Abstract

Natural killer (NK) cells are attractive candidates for allogeneic cell-based immunotherapy due to their potent antitumor effector function and good safety profile. NK cells express killer immunoglobulin-like receptors (KIRs) and the NKG2A receptor important for NK cells education as well as providing inhibitory signals upon encountering HLA-expressing target cells. Multiple myeloma (MM) is an example of a tumor expressing relatively high levels of HLA molecules. In this review, we discuss the functional relevance of inhibitory KIRs and NKG2A for NK cells anti-MM response and strategies to lower these inhibitory signaling to enhance clinical efficacy of allogeneic NK cells in MM.

Original language	English
Article number	2848
Number of pages	8
Journal	Frontiers in Immunology
Volume	9
DOIs	https://doi.org/10.3389/fimmu.2018.02848
Publication status	Published - 4 Dec 2018

Keywords

NK cell
NKG2A
KIR
HLA class I
HLA-E
multiple myeloma
immunotherapy
HLA CLASS-I
NK CELLS
MEDIATED LYSIS
CYTOTOXICITY RECEPTORS
MISSING SELF
PHASE-I
TRANSPLANTATION
LIGANDS
POLYMORPHISM
EXPRESSION

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Cite this

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title = "Tuning Natural Killer Cell Anti-multiple Myeloma Reactivity by Targeting Inhibitory Signaling via KIR and NKG2A",

abstract = "Natural killer (NK) cells are attractive candidates for allogeneic cell-based immunotherapy due to their potent antitumor effector function and good safety profile. NK cells express killer immunoglobulin-like receptors (KIRs) and the NKG2A receptor important for NK cells education as well as providing inhibitory signals upon encountering HLA-expressing target cells. Multiple myeloma (MM) is an example of a tumor expressing relatively high levels of HLA molecules. In this review, we discuss the functional relevance of inhibitory KIRs and NKG2A for NK cells anti-MM response and strategies to lower these inhibitory signaling to enhance clinical efficacy of allogeneic NK cells in MM.",

keywords = "NK cell, NKG2A, KIR, HLA class I, HLA-E, multiple myeloma, immunotherapy, HLA CLASS-I, NK CELLS, MEDIATED LYSIS, CYTOTOXICITY RECEPTORS, MISSING SELF, PHASE-I, TRANSPLANTATION, LIGANDS, POLYMORPHISM, EXPRESSION",

author = "Mahaweni, \{Niken M.\} and Ehlers, \{Femke A. I.\} and Bos, \{Gerard M. J.\} and Lotte Wieten",

year = "2018",

month = dec,

day = "4",

doi = "10.3389/fimmu.2018.02848",

language = "English",

volume = "9",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Media S.A.",

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TY - JOUR

T1 - Tuning Natural Killer Cell Anti-multiple Myeloma Reactivity by Targeting Inhibitory Signaling via KIR and NKG2A

AU - Mahaweni, Niken M.

AU - Ehlers, Femke A. I.

AU - Bos, Gerard M. J.

AU - Wieten, Lotte

PY - 2018/12/4

Y1 - 2018/12/4

N2 - Natural killer (NK) cells are attractive candidates for allogeneic cell-based immunotherapy due to their potent antitumor effector function and good safety profile. NK cells express killer immunoglobulin-like receptors (KIRs) and the NKG2A receptor important for NK cells education as well as providing inhibitory signals upon encountering HLA-expressing target cells. Multiple myeloma (MM) is an example of a tumor expressing relatively high levels of HLA molecules. In this review, we discuss the functional relevance of inhibitory KIRs and NKG2A for NK cells anti-MM response and strategies to lower these inhibitory signaling to enhance clinical efficacy of allogeneic NK cells in MM.

AB - Natural killer (NK) cells are attractive candidates for allogeneic cell-based immunotherapy due to their potent antitumor effector function and good safety profile. NK cells express killer immunoglobulin-like receptors (KIRs) and the NKG2A receptor important for NK cells education as well as providing inhibitory signals upon encountering HLA-expressing target cells. Multiple myeloma (MM) is an example of a tumor expressing relatively high levels of HLA molecules. In this review, we discuss the functional relevance of inhibitory KIRs and NKG2A for NK cells anti-MM response and strategies to lower these inhibitory signaling to enhance clinical efficacy of allogeneic NK cells in MM.

KW - NK cell

KW - NKG2A

KW - KIR

KW - HLA class I

KW - HLA-E

KW - multiple myeloma

KW - immunotherapy

KW - HLA CLASS-I

KW - NK CELLS

KW - MEDIATED LYSIS

KW - CYTOTOXICITY RECEPTORS

KW - MISSING SELF

KW - PHASE-I

KW - TRANSPLANTATION

KW - LIGANDS

KW - POLYMORPHISM

KW - EXPRESSION

U2 - 10.3389/fimmu.2018.02848

DO - 10.3389/fimmu.2018.02848

M3 - (Systematic) Review article

C2 - 30564241

SN - 1664-3224

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 2848

ER -

Tuning Natural Killer Cell Anti-multiple Myeloma Reactivity by Targeting Inhibitory Signaling via KIR and NKG2A

Abstract

Keywords

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