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NK cells as powerful therapeutic tool in cancer immunotherapy

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Abstract

Background

Natural killer (NK) cells have gained considerable attention and hold great potential for their application in tumor immunotherapy. This is mainly due to their MHC-unrestricted and pan-specific recognition capabilities, as well as their ability to rapidly respond to and eliminate target cells. To artificially generate therapeutic NK cells, various materials can be utilized, such as peripheral blood mononuclear cells (PBMCs), umbilical cord blood (UCB), induced pluripotent stem cells (iPSCs), and NK cell lines. Exploiting the therapeutic potential of NK cells to treat tumors through in vivo and in vitro therapeutic modalities has yielded positive therapeutic results.

Conclusion

This review provides a comprehensive description of NK cell therapeutic approaches for tumors and discusses the current problems associated with these therapeutic approaches and the prospects of NK cell therapy for tumors.

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Data availability

All data obtained and/or analyzed in this study were available from the corresponding author upon reasonable request.

Abbreviations

5T4:

Trophoblast glycoprotein

ADCC:

Antibody-dependent cytotoxicity

ALL:

Acute lymphoblastic leukemia

AKT:

Protein kinase B

AML:

Acute myeloid leukemia

B7-H6:

B7 homolog 6

BAT3:

HLA-B associated transcript 3

BCMA:

B cell maturation antigen

BiKE:

Bi-specific NK cell engagers

C1q:

Complement component 1q

CAR:

Chimeric antigen receptor

CCL:

Chemokine (C-C motif) ligand

CD:

Cluster of differentiation

CEA:

Carcinoembryonic antigen

CEACAM1:

Carcinoembryonic antigen-associated cell adhesion molecule-1

CFP:

Complement factor P

CLL:

Chronic lymphocytic leukemia

CLL1:

C-type lectin-like molecule-1

CIML NK:

Cytokine-induced memory-like NK cell

CISH:

Cytokine-inducible SH2-containing protein

CMV:

CytoMegalo Virus

CR:

Complete response

CRACC:

CD2-like receptor-activating cytotoxic cell

CRS:

Cytokine release syndrome

CRTAM:

Cytotoxic and regulatory T cell molecule

CT26:

Colon tumor 26

CTL:

Cytotoxic T lymphocyte

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

DC:

Dendritic cell

DLIs:

Donor lymphocyte infusions

DLL3:

Delta-like ligand-3

DNAM1:

DNAX accessory molecule-1

DSGb5:

Disialosylglobopentaose

EGFR:

Epidermal growth factor receptor

Epa:

Epithelial adhesin

ERK:

Extracellular signal-regulated kinase

ESC:

Embryonic stem cell

EV:

Extracellular Vesicle

FcγRIIIA:

Fc gamma receptor IIIA

FGL1:

Fibrinogen-like protein 1

FOXO1:

Forkhead box protein O1

GD:

Ganglioside

GNLY:

Granulysin

GzmA/B:

Granzyme A/B

HA:

Hemagglutinin

HCMV:

Human Cytomegalovirus

HN:

Hemagglutinin-neuraminidase

HNSCC:

Head and neck squamous cell carcinoma

HSPG:

Heparan sulfate proteoglycans

FasL:

Fas ligand

FDA:

Food and drug administration

FGL1:

Fibrinogen-like protein 1

FLT3L:

FMS-like tyrosine kinase 3 receptor ligand

Foxo1:

Forkhead box protein O1

Gal9:

Galectin 9

GBM:

Glioblastoma multiforme

GM-CSF:

Granulocyte-macrophage colony stimulating factor

GVHD:

Graft-versus-host disease

haNK cell:

High-affinity NK cell

HCC:

Hepatocellular carcinoma

HCT:

Hematopoietic cell transplantation

HER2:

Human epidermal growth factor receptor 2

HIF:

Hypoxia-inducible factor

HLA:

Human leukocyte antigen

HMGB1:

High mobility group protein 1

HNSCC:

Head and neck squamous cell carcinoma

HSPCs:

Hematopoietic stem cells

HSPG:

Heparan sulfate proteoglycan

IgV:

Immunoglobulin variable region

LAG3:

Lymphocyte activation gene 3

LAIR-1:

Leucocyte-associated immunoglobulin-like receptor-1

LIRs:

Leukocyte immunoglobulin-like receptors

LLT-1:

Lectin-like transcript 1

LSECtin:

Liver sinusoidal endothelial cell lectin

ICI:

Immune checkpoint inhibitor

IFN:

Interferon

IL:

Interleukin

ILT2:

Ig-like transcript 2

IRp60:

Inhibitory receptor protein 60

iPSCs:

Induced Pluripotent stem cells

irAEs:

Immune-related adverse events

ITIM:

Immunoreceptor tyrosine inhibitory motif

JAK:

Janus kinase

KIR:

The killer cell immunoglobulin-like receptor

KLRG1:

Co-inhibitory receptor killer-cell lectin like receptor G1

LAG-3:

Lymphocyte activation gene-3

mAb:

Monoclonal Antibody

mAGP:

Mycolyl-arabinogalactan-peptidoglycan

MAPK:

Mitogen-activated protein kinase

MDS:

Myelodysplastic syndromes

MDSC:

Myeloid-derived suppressor cell

METTL3:

Methyltransferase-like 3

MICA:

MHC class I polypeptide-related sequence A

MICB:

MHC class I polypeptide-related sequence B

MHC:

Major histocompatibility complex

MLL5:

Mixed lineage leukemia 5

MM:

Multiple myeloma

MSLN:

Mesothelin

MUC:

Mucin

mTOR:

Mammalian target of rapamycin

NCRs:

Natural cytotoxicity receptors

NECL2:

Nectin-like protein 2

NEJM:

New England Journal of Medicine

NETs:

Neutrophil extracellular traps

NHL:

Non-Hodgkin lymphoma

NID1:

Nidogen-1

NKCE:

NK cell engagers

NK cell:

Natural killer cell

NKG2:

Nature-killer group 2

NKP:

NK precursor cells

NKp30/44/46:

Natural cytotoxicity receptor 30/44/46

NKRP1A:

Natural killer cell receptor-P1A

NSCLC:

Non-small cell lung cancer

NTB-A:

NK-T-B-antigen

oHSV:

Oncolytic herpes simplex virus

OV:

Oncolytic virus

PBMCs:

Peripheral blood mononuclear cells

PCNA:

Proliferating cell nuclear antigen

PD-1:

Programmed cell death protein 1

PDGF:

Platelet-derived growth factor

PE:

Phosphatidylethanolamine

PfEMP-1:

Plasmodium falciparum erythrocyte membrane protein 1

PFN:

Perforin

PI3K:

Phosphoinositide 3-kinase

PGE2:

Prostaglandin E2

PS:

Phosphatidylserine

PSCA:

Prostate stem cell antigen

PSMA:

Prostate specific membrane antigen

Ptdser:

Phospholipid serine

PVR:

Poliovirus receptor

PVRL2:

Poliovirus receptor related2

rhIL-15:

Recombinant human interleukin-15

ROBO1:

Roundabout guidance receptor 1

SCF:

Stem cell factor

scFv:

Single-chain variable fragment

SHP:

Src homology region 2 domain-containing phosphatase

Siglec:

Sialic acid-binding immunoglobulin-like lectins

siRNA:

Small interfering RNA

STAT1:

Signal transducer and activator of transcription 1

TCRs:

T-cell receptors

TIGIT:

T-cell immunoreceptor with Ig and ITIM domains

TIM-3:

T cell immunoglobulin domain and mucin domain-containing protein 3

TME:

Tumor microenvironment

TNF:

Tumor necrosis factor

TRAIL:

Tumor necrosis factor-associated apoptosis-inducing ligand

TriKE:

Tri-specific NK cell engagers

UCB:

Umbilical cord blood

ULBP:

UL16-binding protein

VAP-1:

Vascular adhesion protein-

VEGFR2:

Vascular endothelial growth factor receptor 2

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Acknowledgements

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Funding

This work has been supported by the National Natural Science Foundation of China (82203163), the Natural Science Foundation of Hunan Province (2022JJ40660), the Natural Science Foundation of Changsha (kq2202123) and open sharing fund for the large-scale instruments and equipments of Central South University (CSUZC202235).

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Authors and Affiliations

  1. NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, China

    Mao Huang, Yixuan Liu, Miao Peng, Junshang Ge, Yongzhen Mo, Zhaoyang Zeng, Chunmei Fan & Wei Xiong

  2. Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China

    Mao Huang, Yixuan Liu, Miao Peng, Junshang Ge, Yongzhen Mo, Fuyan Wang, Zhaoyang Zeng, Chunmei Fan & Wei Xiong

  3. Department of Pathology, Xiangya Hospital, Central South University, 410078, Changsha, Hunan, China

    Qijia Yan

  4. Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 410078, Changsha, Hunan, China

    Yumin Wang

  5. Department of Medicine, Comprehensive Cancer Center, Baylor College of Medicine, Alkek Building, RM N720, Houston, TX, USA

    Yong Li

  6. Department of Histology and Embryology, Xiangya School of Medicine, Central South University, 410013, Changsha, Hunan Province, China

    Chunmei Fan

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  1. Mao Huang
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Contributions

MH, YXL, MP, JSG, YZM, YMW contributed to drafting and editing the manuscript and figures. WX, ZYZ and CMF designed, revised, and finalized the manuscript. YL and ZYZ participated in the design of this review. QJY and FYW contributed to the literature search. All authors contributed toward drafting and revising and agreed to submit.

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Huang, M., Liu, Y., Yan, Q. et al. NK cells as powerful therapeutic tool in cancer immunotherapy. Cell Oncol. 47, 733–757 (2024). https://doi.org/10.1007/s13402-023-00909-3

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