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
. 2024 Jan 22;22(1):59.
doi: 10.1186/s12964-023-01428-2.

The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia

Asal Barshidi #  1 , Keivan Ardeshiri #  2 , Farbod Ebrahimi  3 , Fatemeh Alian  4 , Ali Akbar Shekarchi  5 , Mohammad Hojjat-Farsangi  6 , Farhad Jadidi-Niaragh  7   8   9
Affiliations
Review

The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia

Asal Barshidi et al. Cell Commun Signal. .

Abstract

The immune responses to cancer cells involve both innate and acquired immune cells. In the meantime, the most attention has been drawn to the adaptive immune cells, especially T cells, while, it is now well known that the innate immune cells, especially natural killer (NK) cells, play a vital role in defending against malignancies. While the immune cells are trying to eliminate malignant cells, cancer cells try to prevent the function of these cells and suppress immune responses. The suppression of NK cells in various cancers can lead to the induction of an exhausted phenotype in NK cells, which will impair their function. Recent studies have shown that the occurrence of this phenotype in various types of leukemic malignancies can affect the prognosis of the disease, and targeting these cells may be considered a new immunotherapy method in the treatment of leukemia. Therefore, a detailed study of exhausted NK cells in leukemic diseases can help both to understand the mechanisms of leukemia progression and to design new treatment methods by creating a deeper understanding of these cells. Here, we will comprehensively review the immunobiology of exhausted NK cells and their role in various leukemic malignancies. Video Abstract.

Keywords: Cancer; Exhaustion; Hematopoietic malignancies; Leukemia; Natural killer cells.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Phenotypic and functional properties of NK cells in cancer. While immunosuppressive cells or cytokines, exosomes, and hypoxia promote exhaustion of NK cells, chemotherapy, stimulatory cytokines, blockade of immune checkpoint molecules, and stimulating activating receptors prevent exhaustion
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Bi J, Tian Z. NK cell exhaustion. Front Immunol. 2017;8:760. doi: 10.3389/fimmu.2017.00760. - DOI - PMC - PubMed
    1. Zhang Q, et al. Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity. Nat Immunol. 2018;19(7):723–732. doi: 10.1038/s41590-018-0132-0. - DOI - PubMed
    1. Ishigami S, et al. Clinical impact of intratumoral natural killer cell and dendritic cell infiltration in gastric cancer. Cancer Lett. 2000;159(1):103–108. doi: 10.1016/S0304-3835(00)00542-5. - DOI - PubMed
    1. Peng LS, et al. Tumor-Associated Monocytes/Macrophages Impair NK-Cell Function via TGFβ1 in Human Gastric Cancer. Cancer Immunol Res. 2017;5(3):248–256. doi: 10.1158/2326-6066.CIR-16-0152. - DOI - PubMed
    1. Merino AM, et al. Unraveling exhaustion in adaptive and conventional NK cells. J Leukoc Biol. 2020;108(4):1361–1368. doi: 10.1002/JLB.4MR0620-091R. - DOI - PMC - PubMed