Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 May 23;20(1):240.
doi: 10.1186/s12967-022-03437-0.

Natural killer cells: a promising immunotherapy for cancer

Junfeng Chu #  1 , Fengcai Gao #  2 , Meimei Yan #  1 , Shuang Zhao  1 , Zheng Yan  1 , Bian Shi  3 , Yanyan Liu  4
Affiliations
Review

Natural killer cells: a promising immunotherapy for cancer

Junfeng Chu et al. J Transl Med. .

Abstract

As a promising alternative platform for cellular immunotherapy, natural killer cells (NK) have recently gained attention as an important type of innate immune regulatory cell. NK cells can rapidly kill multiple adjacent cancer cells through non-MHC-restrictive effects. Although tumors may develop multiple resistance mechanisms to endogenous NK cell attack, in vitro activation, expansion, and genetic modification of NK cells can greatly enhance their anti-tumor activity and give them the ability to overcome drug resistance. Some of these approaches have been translated into clinical applications, and clinical trials of NK cell infusion in patients with hematological malignancies and solid tumors have thus far yielded many encouraging clinical results. CAR-T cells have exhibited great success in treating hematological malignancies, but their drawbacks include high manufacturing costs and potentially fatal toxicity, such as cytokine release syndrome. To overcome these issues, CAR-NK cells were generated through genetic engineering and demonstrated significant clinical responses and lower adverse effects compared with CAR-T cell therapy. In this review, we summarize recent advances in NK cell immunotherapy, focusing on NK cell biology and function, the types of NK cell therapy, and clinical trials and future perspectives on NK cell therapy.

Keywords: CAR-NK cells; Cancer; Immunotherapy; NK cells.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest relating to the publication of this manuscript.

Figures

Fig.  1
Fig.  1
Schematic diagram of tumor-infiltrating immune cells interactions among each other and with cancer cells. Innate immune response cells (macrophages, mast cells and neutrophils) and adaptive immune response cells (lymphocytes) interact with tumor cells through chemokines, adipose cytokines and cytokines
Fig.  2
Fig.  2
NK cell development. In mice, common lymphoid progenitor (CLP) produces common ILC precursor, CILCP). CILCP can produce NK cells and helper-like ILCs. There are at least five other stages in NK cell development from CILCP: NK progenitor cells (NKP), refined-NKP (rNKP), CD27+CD11b−NK, CD27+CD11b+NK and CD27−CD11b+ NK. In humans, after CILCP is developed from CLP, NK-restricted NKP will be developed from the latter. NKs is characterized by expressing CD122, losing CD34 and CD127. The expression of T-bet and Eomes is needed for further differentiation into functional NK cells. The expression of CD56 can divide NK cells into two subgroups: CD56dim and CD56bright. The two subsets express activated surface receptors NKp46 and NKp80. CD56+ NK cells can differentiate into CD56− NK cells by expressing CD16, PEN5 and CD57
Fig.  3
Fig.  3
NK cells in tumor immunosurveillance. This figure shows the potential role of NK cells in tumor immunosurveillance. NK cells initially recognize tumor cells through stress or danger signals. Activated NK cells directly kill target tumor cells through at least four mechanisms: cytoplasmic granule release, death receptor-induced apoptosis, effector molecule production, or ADCC. In addition, NK cells interact as regulatory cells with dendritic cells to improve their antigen uptake and presentation and promote the generation of antigen-specific CTL responses. Also, activated NK cells induce CD8+ T cells to become CTLs by producing cytokines such as IFN-γ. Activated NK cells also promote CD4+ T cells to differentiate toward Th1 responses and promote CTL differentiation. Cytokines produced by NK cells may also regulate the production of anti-tumor antibodies by B cells. Abs, antibodies; ADCC, antibody-dependent cellular cytotoxicity; CTL, cytotoxic T lymphocyte; DC, dendritic cell; IFN, interferon; NK, natural killer
Fig.  4
Fig.  4
NK cell-based therapeutic strategies. A Autologous NK cell transfer:Cytokines IL-2, IL-12,IL-15, IL-18, as well as IL-21 in vitro can stimulate NK cells from patients’ blood and promote in vivo NK-cells proliferation and activation after NK cells are infused into cancer patients. NK cells release perforin, as well as granzyme, to cause apoptosis of tumor cells after they contact and recognize receptor on the tumor cells. B Allogeneic NK cell transfer: NK cells from healthy donors’ peripheral cord blood expand in vitro and are infused into cancer patients. NK cells with donor KIR release perforin, as well as granzyme, to cause apoptosis of tumor cells after they contact and recognize HLA receptor on the tumor cells. If KIR-ligand mismatch, no negative signal exists. C CAR-engineered NK cells: There are four different generations of CARs and they deliver stimulation signals to NK cells. Through genetic engineering modification, CAR can bind to tumor specific antigens are expressed on the surface of NK cells. After transfusion, tumor cells with specific antigens can be specifically recognized and immune responses can be triggered to achieve the purpose of tumor cell clearance
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33. doi: 10.3322/caac.21654. - DOI - PubMed
    1. Canfell K, Kim JJ, Brisson M, et al. Mortality impact of achieving WHO cervical cancer elimination targets: a comparative modelling analysis in 78 low-income and lower-middle-income countries. Lancet. 2020;395(10224):591–603. doi: 10.1016/S0140-6736(20)30157-4. - DOI - PMC - PubMed
    1. Hutchinson MKND, Mierzwa M, D’Silva NJ. Radiation resistance in head and neck squamous cell carcinoma: dire need for an appropriate sensitizer. Oncogene. 2020;39(18):3638–3649. doi: 10.1038/s41388-020-1250-3. - DOI - PMC - PubMed
    1. Garcia-Mayea Y, Mir C, Masson F, Paciucci R, Leonart ME. Insights into new mechanisms and models of cancer stem cell multidrug resistance. Semin Cancer Biol. 2020;60:166–180. doi: 10.1016/j.semcancer.2019.07.022. - DOI - PubMed
    1. Min HY, Lee HY. Mechanisms of resistance to chemotherapy in non-small cell lung cancer. Arch Pharm Res. 2021;44(2):146–164. doi: 10.1007/s12272-021-01312-y. - DOI - PubMed

Publication types

Substances