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Original Article | Open Access

Expression of KLRG1 on subpopulations of lymphocytes in the peripheral blood of patients with locally advanced nasopharyngeal carcinoma and prognostic analysis

Hengjun Qian1,2, Danning Dong1,2, Peiwen Fan1,2, Yaning Feng1,2, Yanchun Peng4, Xuan Yao4, Ruozheng Wang1,2,3( )
Chinese Academy of Medical Sciences Key Laboratory of Cancer Immunotherapy and Radiotherapy, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
Xinjiang Key Laboratory of Oncology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China
Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, Oxfordshire, UK

Hengjun Qian and Danning Dong contributed equally to this study.

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Abstract

Objective

We aimed to investigate the relationship between the expression of killer cell lectin like receptor G1 (KLRG1) in peripheral blood lymphocytes, and the clinical characteristics and prognosis in patients with locally advanced nasopharyngeal carcinoma (NPC), and to dynamically evaluate the changes of KLRG1 expression after treatment.

Methods

A total of 82 patients with locally advanced NPC and 44 healthy individuals were recruited in this study. The expression of KLRG1 on T, natural killer, and natural killer T cells in peripheral blood mononuclear cells (PBMCs) was detected by flow cytometry. Its relationship with clinical characteristics and prognosis of patients, as well as changes in KLRG1 expression in PBMCs after treatment, were investigated.

Results

The expression of KLRG1 in CD8+ T cells in PBMCs of NPC patients was 46.50 (29.10, 69.80)%, significantly higher than 32.50 (17.38, 61.00) % in healthy controls (Z = −2.290, p = 0.022). The expression of KLRG1 in CD3+ CD56+ natural killer T cells in PBMCs of patients was 29.50 (6.21, 78.00) %, significantly higher than 1.47 (0.62, 8.88)% in healthy controls (Z = −5.371, p < 0.001). The expression levels of KLRG1(+)CD8+ T cells in PBMCs of patients were higher in the age ≥50 years (Z = −3.413, p < 0.001), pathology of keratinizing squamous cell carcinoma (H = 10.541, p = 0.005, and EGFR(+) groups (Z = −2.006, p = 0.043). Patients with higher KLRG1(+) expression in CD8+ T cells had a lower progression-free survival (p = 0.029) and a lower distant metastasis-free survival (p = 0.023). KLRG1 expression on T cells increased after radiotherapy.

Conclusion

KLRG1 can be harnessed as a potential target in designing novel therapy to encompass a broader range of NPC patients.

Keywords

immunotherapyprognosisnasopharyngeal carcinomakiller cell lectin-like receptor G1

References

1

Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71(3): 209-249.
Crossref Google Scholar
2

Chen YP, Chan ATC, Le QT, Blanchard P, Sun Y, Ma J. Nasopharyngeal carcinoma. Lancet. 2019; 394(10192): 64-80.
Crossref Google Scholar
3

Wang FH, Wei XL, Feng J, et al. Efficacy, safety, and correlative biomarkers of toripalimab in previously treated recurrent or metastatic nasopharyngeal carcinoma: A Phase II Clinical Trial (POLARIS-02). J Clin Oncol. 2021; 39(7): 704-712.
Crossref Google Scholar
4
Mai HQ, Chen QY, Chen D, et al. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med. 2021; 27(9): 1536-1543. [published correction appears in Nat Med. 2022 Jan; 28(1): 214]
5

Voehringer D, Koschella M, Pircher H. Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1). Blood. 2002; 100(10): 3698-3702.
Crossref Google Scholar
6

Yuzefpolskiy Y, Baumann FM, Kalia V, Sarkar S. Early CD8 T-cell memory precursors and terminal effectors exhibit equipotent in vivo degranulation. Cell Mol Immunol. 2015; 12(4): 400-408.
Crossref Google Scholar
7

Akbar AN, Henson SM, Lanna A. Senescence of T lymphocytes: Implications for enhancing human immunity. Trends Immunol. 2016; 37(12): 866-876.
Crossref Google Scholar
8

Lugli E, Dominguez MH, Gattinoni L, et al. Superior T memory stem cell persistence supports long-lived T cell memory. J Clin Invest. 2013; 123(2): 594-599.
Crossref Google Scholar
9

Dong DN, Fan PW, Feng YN, et al. Association between circulating CD39+CD8+ T cells pre-chemoradiotherapy and prognosis in patients with nasopharyngeal carcinoma. Chin Med J (Engl). 2021; 134(17): 2066-2072.
Crossref Google Scholar
10

Hu Z, Zhao HM, Li CL, et al. The role of KLRG1 in human CD4+ T-cell immunity against tuberculosis. J Infect Dis. 2018; 217(9): 1491-1503.
Crossref Google Scholar
11

Wijaya RS, Read SA, Schibeci S, et al. KLRG1+ natural killer cells exert a novel antifibrotic function in chronic hepatitis B. J Hepatol. 2019; 71(2): 252-264.
Crossref Google Scholar
12

Wang JM, Cheng YQ, Shi L, et al. KLRG1 negatively regulates natural killer cell functions through the Akt pathway in individuals with chronic hepatitis C virus infection. J Virol. 2013; 87(21): 11626-11636.
Crossref Google Scholar
13

Guo Y, Feng Y, Fan P, et al. Expression and clinical significance of KLRG1 and 2B4 on T cells in the peripheral blood and tumour of patients with cervical cancer. Immunol Invest. 2022; 51(3): 670-687.
Crossref Google Scholar
14

Saleh R, Taha RZ, Toor SM, et al. Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer. Cancer Immunol Immunother. 2020; 69(10): 1989-1999.
Crossref Google Scholar
15

Rosshart S, Hofmann M, Schweier O, et al. Interaction of KLRG1 with E-cadherin: new functional and structural insights. Eur J Immunol. 2008; 38(12): 3354-3364.
Crossref Google Scholar
16

Henson SM, Franzese O, Macaulay R, et al. KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells. Blood. 2009; 113(26): 6619-6628.
Crossref Google Scholar
17

Cyktor JC, Carruthers B, Stromberg P, Flaño E, Pircher H, Turner J. Killer cell lectin-like receptor G1 deficiency significantly enhances survival after Mycobacterium tuberculosis infection. Infect Immun. 2013; 81(4): 1090-1099.
Crossref Google Scholar
18

Schwartzkopff S, Gründemann C, Schweier O, et al. Tumor-associated E-cadherin mutations affect binding to the killer cell lectin-like receptor G1 in humans. J Immunol. 2007; 179(2): 1022-1029.
Crossref Google Scholar
19

Liou AK, Soon G, Tan L, et al. Elevated IL18 levels in Nasopharyngeal carcinoma induced PD-1 expression on NK cells in TILS leading to poor prognosis. Oral Oncol. 2020; 104: 104616. doi:10.1016/j.oraloncology.2020.104616
Crossref Google Scholar
20

Yuling H, Ruijing X, Li L, et al. EBV-induced human CD8+ NKT cells suppress tumorigenesis by EBV-associated malignancies. Cancer Res. 2009; 69(20): 7935-7944.
Crossref Google Scholar
21

Li L, Wan S, Tao K, Wang G, Zhao E. KLRG1 restricts memory T cell antitumor immunity. Oncotarget. 2016; 7(38): 61670-61678.
Crossref Google Scholar
22

Apetoh L, Smyth MJ, Drake CG, et al. Consensus nomenclature for CD8+ T cell phenotypes in cancer. Oncoimmunology. 2015; 4(4): e998538. doi:10.1080/2162402X.2014.998538
Crossref Google Scholar
23

Vazquez A, Khan MN, Govindaraj S, Baredes S, Eloy JA. Nasopharyngeal squamous cell carcinoma: a comparative analysis of keratinizing and nonkeratinizing subtypes. Int Forum Allergy Rhinol. 2014; 4(8): 675-683.
Crossref Google Scholar
24

Chatterjee B, Deng Y, Holler A, et al. CD8+ T cells retain protective functions despite sustained inhibitory receptor expression during Epstein–Barr virus infection in vivo. PLoS Pathog. 2019; 15(5): e1007748. doi:10.1371/journal.ppat.1007748
Crossref Google Scholar
25

Ferrara R, Naigeon M, Auclin E, et al. Circulating T-cell immunosenescence in patients with advanced non-small cell lung cancer treated with single-agent PD-1/PD-L1 inhibitors or platinum-based chemotherapy. Clin Cancer Res. 2021; 27(2): 492-503.
Crossref Google Scholar
26

Kuss I, Hathaway B, Ferris RL, Gooding W, Whiteside TL. Decreased absolute counts of T lymphocyte subsets and their relation to disease in squamous cell carcinoma of the head and neck. Clin Cancer Res. 2004; 10(11): 3755-3762.
Crossref Google Scholar
27

Parikh F, Duluc D, Imai N, et al. Chemoradiotherapy-induced upregulation of PD-1 antagonizes immunity to HPV-related oropharyngeal cancer. Cancer Res. 2014; 74(24): 7205-7216
Crossref Google Scholar
28

van Meir H, Nout RA, Welters MJ, et al. Impact of (chemo)radiotherapy on immune cell composition and function in cervical cancer patients. Oncoimmunology. 2016; 6(2): e1267095. doi:10.1080/2162402X.2016.1267095
Crossref Google Scholar
29

Rotte A. Combination of CTLA-4 and PD-1 blockers for treatment of cancer. J Exp Clin Cancer Res. 2019; 38(1): 255.
Crossref Google Scholar
30

Kleffel S, Posch C, Barthel SR, et al. Melanoma cell-intrinsic PD-1 receptor functions promote tumor growth. Cell. 2015; 162(6): 1242-1256.
Crossref Google Scholar
31

Kang CW, Dutta A, Chang LY, et al. Apoptosis of tumor infiltrating effector TIM-3+CD8+ T cells in colon cancer. Sci Rep. 2015; 5: 15659. doi:10.1038/srep15659
Crossref Google Scholar
32

Greenberg SA, Kong SW, Thompson E, Gulla SV. Co-inhibitory T cell receptor KLRG1: human cancer expression and efficacy of neutralization in murine cancer models. Oncotarget. 2019; 10(14): 1399-1406.
Crossref Google Scholar
33

Tata A, Dodard G, Fugère C, et al. Combination blockade of KLRG1 and PD-1 promotes immune control of local and disseminated cancers. Oncoimmunology. 2021; 10(1): 1933808. doi:10.1080/2162402X.2021.1933808
Crossref Google Scholar
Precision Radiation Oncology
Volume 6 Issue 3,
September 2022
Pages 199-208
DOI: 10.1002/pro6.1165
Cite this article:
Qian H, Dong D, Fan P, et al. Expression of KLRG1 on subpopulations of lymphocytes in the peripheral blood of patients with locally advanced nasopharyngeal carcinoma and prognostic analysis. Precision Radiation Oncology, 2022, 6(3): 199-208. https://doi.org/10.1002/pro6.1165

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Received: 06 April 2022
Revised: 16 June 2022
Accepted: 21 June 2022
Published: 16 July 2022
© 2022 The Authors. Precision Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Shandong Cancer Hospital & Institute.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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