Changes in Subset Distribution and Impaired Function of Circulating Natural Killer Cells in Patients with Colorectal Cancer

Overview

Journal Sci Rep

Specialty Science

Date 2024 May 28

PMID 38806640

Authors

Shujin Zu

Yan Lu

Rui Xing

Xiang Chen

Longyi Zhang

Affiliations

Soon will be listed here.

Abstract

Natural killer (NK) cells are closely associated with malignant tumor progression and metastasis. However, studies on their relevance in colorectal cancer (CRC) are limited. We aimed to comprehensively analyze the absolute counts, phenotypes, and function of circulating NK cells in patients with CRC using multiparametric flow cytometry. The distribution of NK cell subsets in the peripheral circulation of patients with CRC was significantly altered relative to the control group. This is shown by the decreased frequency and absolute count of CD56CD16 NK cells with antitumor effects, contrary to the increased frequency of CD56 NK and CD56CD16 NK cells with poor or ineffective antitumor effects. NK cells in patients with CRC were functionally impaired, with decreased intracellular interferon (IFN)-γ secretion and a significantly lower percentage of cell surface granzyme B and perforin expression. In addition, IFN-γ expression decreased significantly with the tumor stage progression. Based on a comprehensive analysis of the absolute counts, phenotypes, and functional markers of NK cells, we found an altered subset distribution and impaired function of circulating NK cells in patients with CRC.

References

De Maria A, Bozzano F, Cantoni C, Moretta L . Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-gamma on activation. Proc Natl Acad Sci U S A. 2010; 108(2):728-32. PMC: 3021076. DOI: 10.1073/pnas.1012356108. View

Stabile H, Nisti P, Pagliara D, Locatelli F, Santoni A, Gismondi A . Response to comment on Multifunctional human CD56low CD16low NK cells are the prominent subset in bone marrow of both pediatric healthy donors and leukemic patients. Haematologica. 2015; 100(8):e332-3. PMC: 5004438. DOI: 10.3324/haematol.2015.130831. View

Vujanovic L, Chuckran C, Lin Y, Ding F, Sander C, Santos P . CD56 CD16 Natural Killer Cell Profiling in Melanoma Patients Receiving a Cancer Vaccine and Interferon-α. Front Immunol. 2019; 10:14. PMC: 6361792. DOI: 10.3389/fimmu.2019.00014. View

Juelke K, Killig M, Luetke-Eversloh M, Parente E, Gruen J, Morandi B . CD62L expression identifies a unique subset of polyfunctional CD56dim NK cells. Blood. 2010; 116(8):1299-307. DOI: 10.1182/blood-2009-11-253286. View

Morandi F, Horenstein A, Chillemi A, Quarona V, Chiesa S, Imperatori A . CD56brightCD16- NK Cells Produce Adenosine through a CD38-Mediated Pathway and Act as Regulatory Cells Inhibiting Autologous CD4+ T Cell Proliferation. J Immunol. 2015; 195(3):965-72. DOI: 10.4049/jimmunol.1500591. View

Zhang L, Chen X, Zu S, Lu Y . Characteristics of circulating adaptive immune cells in patients with colorectal cancer. Sci Rep. 2022; 12(1):18166. PMC: 9616942. DOI: 10.1038/s41598-022-23190-0. View

Li Q, Cai S, Li M, Zhou X, Wu G, Kang K . Natural killer cell exhaustion in lung cancer. Int Immunopharmacol. 2021; 96:107764. DOI: 10.1016/j.intimp.2021.107764. View

Mukherjee N, Ji N, Hurez V, Curiel T, Montgomery M, Braun A . Intratumoral CD56 natural killer cells are associated with improved survival in bladder cancer. Oncotarget. 2018; 9(92):36492-36502. PMC: 6284861. DOI: 10.18632/oncotarget.26362. View

Cichocki F, Grzywacz B, Miller J . Human NK Cell Development: One Road or Many?. Front Immunol. 2019; 10:2078. PMC: 6727427. DOI: 10.3389/fimmu.2019.02078. View

10.

Huntington N, Cursons J, Rautela J . The cancer-natural killer cell immunity cycle. Nat Rev Cancer. 2020; 20(8):437-454. DOI: 10.1038/s41568-020-0272-z. View

11.

Cui F, Qu D, Sun R, Zhang M, Nan K . NK cell-produced IFN-γ regulates cell growth and apoptosis of colorectal cancer by regulating IL-15. Exp Ther Med. 2020; 19(2):1400-1406. PMC: 6966233. DOI: 10.3892/etm.2019.8343. View

12.

Tang G, Yuan X, Luo Y, Lin Q, Chen Z, Xing X . Establishing immune scoring model based on combination of the number, function, and phenotype of lymphocytes. Aging (Albany NY). 2020; 12(10):9328-9343. PMC: 7288950. DOI: 10.18632/aging.103208. View

13.

Orange J, Chehimi J, Ghavimi D, Campbell D, Sullivan K . Decreased natural killer (NK) cell function in chronic NK cell lymphocytosis associated with decreased surface expression of CD11b. Clin Immunol. 2001; 99(1):53-64. DOI: 10.1006/clim.2001.5002. View

14.

Hodge G, Barnawi J, Jurisevic C, Moffat D, Holmes M, Reynolds P . Lung cancer is associated with decreased expression of perforin, granzyme B and interferon (IFN)-γ by infiltrating lung tissue T cells, natural killer (NK) T-like and NK cells. Clin Exp Immunol. 2014; 178(1):79-85. PMC: 4360197. DOI: 10.1111/cei.12392. View

15.

Jiang H, Jiang J . Balancing act: the complex role of NK cells in immune regulation. Front Immunol. 2023; 14:1275028. PMC: 10652757. DOI: 10.3389/fimmu.2023.1275028. View

16.

Morgan E, Arnold M, Gini A, Lorenzoni V, Cabasag C, Laversanne M . Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut. 2023; 72(2):338-344. DOI: 10.1136/gutjnl-2022-327736. View

17.

Mota G, Moldovan I, Calugaru A, Hirt M, Kozma E, Galatiuc C . Interaction of human immunoglobulin G with CD16 on natural killer cells: ligand clearance, FcgammaRIIIA turnover and effects of metalloproteinases on FcgammaRIIIA-mediated binding, signal transduction and killing. Scand J Immunol. 2004; 59(3):278-84. DOI: 10.1111/j.0300-9475.2004.01398.x. View

18.

Wang Y, Zhou N, Liu H, Gong X, Zhu R, Li X . Circulating activated lymphocyte subsets as potential blood biomarkers of cancer progression. Cancer Med. 2020; 9(14):5086-5094. PMC: 7367640. DOI: 10.1002/cam4.3150. View

19.

Abedizadeh R, Majidi F, Khorasani H, Abedi H, Sabour D . Colorectal cancer: a comprehensive review of carcinogenesis, diagnosis, and novel strategies for classified treatments. Cancer Metastasis Rev. 2023; 43(2):729-753. DOI: 10.1007/s10555-023-10158-3. View

20.

Wagner J, Rosario M, Romee R, Berrien-Elliott M, Schneider S, Leong J . CD56bright NK cells exhibit potent antitumor responses following IL-15 priming. J Clin Invest. 2017; 127(11):4042-4058. PMC: 5663359. DOI: 10.1172/JCI90387. View