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http://dx.doi.org/10.3340/jkns.2020.0339

Preliminary Study on Natural Killer Cell Activity for Interfer-on-Gamma Production after Gamma Knife Radiosurgery for Brain Tumors  

Park, Kawngwoo (Department of Neurosurgery, Gachon University Gil Medical Center)
Jeong, Sang Soon (Department of Neurosurgery, Seoul National University College of Medicine)
Kim, Jung Hoon (Department of Neurosurgery, Seoul National University College of Medicine)
Chung, Hyun-Tai (Department of Neurosurgery, Seoul National University College of Medicine)
Lee, Eun Jung (Department of Neurosurgery, Seoul National University College of Medicine)
Moon, Hyo Eun (Department of Neurosurgery, Seoul National University College of Medicine)
Park, Kwang Hyon (Department of Neurosurgery, Seoul National University College of Medicine)
Kim, Jin Wook (Department of Neurosurgery, Seoul National University College of Medicine)
Park, Hye Ran (Department of Neurosurgery, Soonchunhyang University Hospital)
Lee, Jae Meen (Department of Neurosurgery, Pusan National University Hospital)
Lee, Hye Ja (Department of R & D, NK MAX Company)
Kim, Hye Rim (Department of R & D, NK MAX Company)
Cho, Yong Hwan (Department of R & D, NK MAX Company)
Paek, Sun Ha (Department of Neurosurgery, Seoul National University College of Medicine)
Publication Information
Journal of Korean Neurosurgical Society / v.65, no.6, 2022 , pp. 861-867 More about this Journal
Abstract
Objective : High-dose radiation is well known to induce and modulate the immune system. This study was performed to evaluate the correlation between clinical outcomes and changes in natural killer cell activity (NKA) after Gamma Knife Radiosurgery (GKS) in patients with brain cancer. Methods : We performed an open-label, prospective, cross-sectional study of 38 patients who were treated with GKS for brain tumors, including metastatic and benign brain tumors. All of the patients underwent GKS, and blood samples were collected before and after GKS. NKA was measured using an enzyme-linked immunosorbent assay kit, to measure interferon-gamma (IFNγ) secreted by ex vivo-stimulated NK cells from whole blood. We explored the correlations between NK cell-produced IFNγ (NKA-IFNγ) levels and clinical parameters of patients who were treated with GKS for brain tumors. Results : NKA-IFNγ levels were decreased in metastatic brain tumor patients compared to those with benign brain tumors (p<0.0001). All the patients who used steroid treatment to reduce brain swelling after GKS had an NKA-IFNγ level of zero except one patient. High NKA-IFNγ levels were not associated with a rapid decrease in brain metastasis and did not increase after GKS. Conclusion : The activity of NK cells in metastatic brain tumors decreased more than that in benign brain tumors after GKS.
Keywords
Natural killer cell; Interferon-gamma; Gamma Knife Radiosurgery;
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1 Nederby L, Jakobsen A, Hokland M, Hansen TF : Quantification of NK cell activity using whole blood: methodological aspects of a new test. J Immunol Methods 458 : 21-25, 2018   DOI
2 Nordmann N, Hubbard M, Nordmann T, Sperduto PW, Clark HB, Hunt MA : Effect of gamma knife radiosurgery and programmed cell death 1 receptor antagonists on metastatic melanoma. Cureus 9 : e1943, 2017
3 Sologuren I, Rodriguez-Gallego C, Lara PC : Immune effects of high dose radiation treatment: implications of ionizing radiation on the development of bystander and abscopal effects. Transl Canc Res 3 : 18-31, 2014
4 Stevens A, Kloter I, Roggendorf W : Inflammatory infiltrates and natural killer cell presence in human brain tumors. Cancer 61 : 738-743, 1988   DOI
5 Szeifert GT, Salmon I, Rorive S, Massager N, Devriendt D, Simon S, et al. : Does gamma knife surgery stimulate cellular immune response to metastatic brain tumors? A histopathological and immunohistochemical study. J Neurosurg 102 Suppl : 180-184, 2005   DOI
6 Vivier E, Ugolini S : Natural killer cells: from basic research to treatments. Front Immunol 2 : 18, 2011
7 Wallin RP, Screpanti V, Michaelsson J, Grandien A, Ljunggren HG : Regulation of perforin-independent NK cell-mediated cytotoxicity. Eur J Immunol 33 : 2727-2735, 2003   DOI
8 Lee SB, Cha J, Kim IK, Yoon JC, Lee HJ, Park SW, et al. : A high-throughput assay of NK cell activity in whole blood and its clinical application. Biochem Biophys Res Commun 445 : 584-590, 2014   DOI
9 Kaur P, Asea A : Radiation-induced effects and the immune system in cancer. Front Oncol 2 : 191, 2012
10 Kipnis J, Filiano AJ : Neuroimmunology in 2017: the central nervous system: privileged by immune connections. Nat Rev Immunol 18 : 83-84, 2018   DOI
11 Luetke-Eversloh M, Killig M, Romagnani C : Signatures of human NK cell development and terminal differentiation. Front Immunol 4 : 499, 2013
12 Nederby L, Hansen T, Raunkilde L, Jensen LH, Jakobsen AKM : Natural killer cell activity: a test for immune reactivity with clinical perspectives. JCO 36 5_suppl : 87, 2018
13 Parney IF : Basic concepts in glioma immunology. Adv Exp Med Biol 746 : 42-52, 2012   DOI
14 Ahn MJ, Lee K, Lee KH, Kim JW, Kim IY, Bae WK : Combination of antiPD-1 therapy and stereotactic radiosurgery for a gastric cancer patient with brain metastasis: a case report. BMC Cancer 18 : 173, 2018   DOI
15 Caligiuri MA : Human natural killer cells. Blood 112 : 461-469, 2008   DOI
16 Cho D, Campana D : Expansion and activation of natural killer cells for cancer immunotherapy. Korean J Lab Med 29 : 89-96, 2009
17 Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, et al. : Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res 15 : 5379-5388, 2009   DOI
18 Dix AR, Brooks WH, Roszman TL, Morford LA : Immune defects observed in patients with primary malignant brain tumors. J Neuroimmunol 100 : 216-232, 1999   DOI
19 Jeong H, Bok S, Hong BJ, Choi HS, Ahn GO : Radiation-induced immune responses: mechanisms and therapeutic perspectives. Blood Res 51 : 157-163, 2016   DOI
20 Poli A, Wang J, Domingues O, Planaguma J, Yan T, Rygh CB, et al. : Targeting glioblastoma with NK cells and mAb against NG2/CSPG4 prolongs animal survival. Oncotarget 4 : 1527-1546, 2013   DOI
21 Schoenhals JE, Seyedin SN, Anderson C, Brooks ED, Li YR, Younes AI, et al. : Uncovering the immune tumor microenvironment in non-small cell lung cancer to understand response rates to checkpoint blockade and radiation. Transl Lung Cancer Res 6 : 148-158, 2017
22 Servadei F, Parente R, Bucci M, Beltrandi E, Tognetti F, Gaist G : Particular features of cell-mediated immunity in patients with anaplastic gliomas. A comparison with kidney and bladder cancer patients. J Neurooncol 1 : 327-332, 1983   DOI
23 Chen J, Liu X, Zeng Z, Li J, Luo Y, Sun W, et al. : Immunomodulation of NK cells by ionizing radiation. Front Oncol 10 : 874, 2020   DOI
24 Jung YS, Kwon MJ, Park DI, Sohn CI, Park JH : Association between natural killer cell activity and the risk of colorectal neoplasia. J Gastroenterol Hepatol 33 : 831-836, 2018   DOI
25 Hatiboglu MA, Kocyigit A, Guler EM, Nalli A, Akdur K, Sakarcan A, et al. : Gamma knife radiosurgery compared to whole brain radiation therapy enhances immunity via immunoregulatory molecules in patients with metastatic brain tumours. Br J Neurosurg 34 : 604-610, 2020   DOI
26 Zhang T, Yu H, Ni C, Zhang T, Liu L, Lv Q, et al. : Hypofractionated stereotactic radiation therapy activates the peripheral immune response in operable stage I non-small-cell lung cancer. Sci Rep 7 : 4866, 2017   DOI
27 Zhi-Feng W, Le-Yuan Z, Xiao-Hui Z, Ya-Bo G, Jian-Ying Z, Yong H, et al. : TLR4-dependent immune response promotes radiation-induced liver disease by changing the liver tissue interstitial microenvironment during liver cancer radiotherapy. Radiat Res 182 : 674-682, 2014   DOI
28 Barkin J, Rodriguez-Suarez R, Betito K : Association between natural killer cell activity and prostate cancer: a pilot study. Can J Uro 24 : 8708-8713, 2017
29 Berghoff AS, Preusser M : The inflammatory microenvironment in brain metastases: potential treatment target? Chin Clin Oncol 4 : 21, 2015
30 Carvalho HA, Villar RC : Radiotherapy and immune response: the systemic effects of a local treatment. Clinics (Sao Paulo) 73(suppl 1) : e557s, 2018   DOI
31 Dahlberg CI, Sarhan D, Chrobok M, Duru AD, Alici E : Natural killer cellbased therapies targeting cancer: possible strategies to gain and sustain anti-tumor activity. Front Immunol 6 : 605, 2015
32 Frey B, Rubner Y, Kulzer L, Werthmoller N, Weiss EM, Fietkau R, et al. : Antitumor immune responses induced by ionizing irradiation and further immune stimulation. Cancer Immunol Immunother 63 : 29-36, 2014   DOI
33 Jobin G, Rodriguez-Suarez R, Betito K : Association between natural killer cell activity and colorectal cancer in high-risk subjects undergoing colonoscopy. Gastroenterology 153 : 980-987, 2017   DOI
34 Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, DvirSzternfeld R, Ulland TK, et al. : A unique Microglia type associated with restricting development of alzheimer's disease. Cell 169 : 1276-1290. e17, 2017   DOI
35 Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. : Structural and functional features of central nervous system lymphatic vessels. Nature 523 : 337-341, 2015   DOI
36 Koo KC, Shim DH, Yang CM, Lee SB, Kim SM, Shin TY, et al. : Reduction of the CD16(-)CD56bright NK cell subset precedes NK cell dysfunction in prostate cancer. PLoS One 8 : e78049, 2013   DOI
37 Lee J, Park KH, Ryu JH, Bae HJ, Choi A, Lee H, et al. : Natural killer cell activity for IFN-gamma production as a supportive diagnostic marker for gastric cancer. Oncotarget 8 : 70431-70440, 2017   DOI
38 Lee SJ, Kang WY, Yoon Y, Jin JY, Song HJ, Her JH, et al. : Natural killer (NK) cells inhibit systemic metastasis of glioblastoma cells and have therapeutic effects against glioblastomas in the brain. BMC Cancer 15 : 1011, 2015   DOI
39 McBride WH, Chiang CS, Olson JL, Wang CC, Hong JH, Pajonk F, et al. : A sense of danger from radiation. Radiat Res 162 : 1-19, 2004   DOI
40 McKelvey KJ, Hudson AL, Back M, Eade T, Diakos CI : Radiation, inflammation and the immune response in cancer. Mamm Genome 29 : 843-865, 2018   DOI