Prognostic value of CD3, CD4, CD8 and CD 68 in high-grade diffuse astrocytomas, the transformation of an immune profile in recurrent tumors

Taisia Chertenko, Irina Yakovtsova

Abstract


Introduction and purpose. Immunotherapy has shown good results in the treatment of other cancers. There is a lack of data about the role of the immune system in high-grade glioma development. Moreover, the available data is ambiguous. Our recent study was aimed to clarify the prognostic value of T-cell and macrophage infiltration in high grade diffuse astrocytic tumors. In addition, we also investigated the changes in immune cell infiltration in paired primary and recurrent tumors. Methods. This study included 45 tumor samples that were collected from 15 patients without recurrence within 1 year after the surgery and from 15 patients who experienced a recurrence within 1 year after the surgery (30 paired samples). Immunohistochemistry with primary antibody CD3, CD4, CD8 and CD68 was used in our study. We marked lack of immune cell infiltration or single cell infiltration as “1” in our study and moderate or high infiltration as “2”. Results. CD68 “2” expression in tumor tissue is a significant independent factor of the worse prognosis (Fisher’s exact p-value=0,037). The significantly better prognosis was given to patients with such immune patterns as CD3 “1”/CD4 “2”/CD8 “2” and CD3 “1”/CD4 “2”/CD68 “2” (Fisher’s exact p-value=0,01869 and 0,01392 respectively). We also found that solid tumors with CD3 “2”/CD8 “1” and CD8 “1”/CD68 “2” immune had a significantly worse prognosis (Fisher’s exact p-value= 0,04981 in both groups). In relapsed tumors, we observed a significant increase of CD8-cell infiltration (McNemar test p-value=0,01343;p <0,05) that probably may be a result of treatment with temozolomide. Conclusion. Our findings confirmed the fact that immune cell infiltration may play an important role in brain tumor development. Further study in larger groups may lead to a better understanding of different immune profiles of glial tumors and to development of their targeted immunotherapy.

Keywords


Glioblastoma; T cells; CD68; paired tumors; immunohistochemistry; prognostic markers

Full Text:

PDF

References


Badie B, Schartner JM (2000) Flow cytometric characterization of tumor-associated macrophages in experimental gliomas. Neurosurgery 46: 957-961 Neurosurgery 46: 957–961

Becher B, Prat A, Antel JP (2000) Brain–immune connection: immuno-regulatory properties of CNS-resident cells. Glia 29: 293–304

Berghoff AS, Kiesel B, Wiedhalm G, Wilhelm D et al. (2017) Correlation of immune phenotype with IDH mutation in diffuse glioma. Neuro-Oncology 19(11):1460–1468. https://doi.org/10.1093/neuonc/nox054

Choi SJ, Hwang HYet al. (2010) The radiologic features of cystic versus noncystic glioblastoma multiforme as significant prognostic factors. J Korean Soc Radiol. 63: 299–306. https://doi.org/10.3348/jksr.2010.63.4.299

Cioca A, Olteanu EG, Gisca MD, Morosanu CO, Marin I, Florian IS (2016) Expression of EGFR in paired new and recurrent glioblastomas. Asian Pac J Cancer Prev. 17(9): 4205–4208

ErberW (2010) Diagnostic Techniques in Hematological Malignancies Cambridge University Press, Cambridge: P. 133

Gomez GG, Kruse CA (2006) Mechanisms of malignant glioma immune resistance and sources of immunosuppression. Gene Ther. Mol. Biol. 10:133–146

Kaur G, Bloch OA (2011) A critical evaluation of cystic features in primary glioblastoma as a prognostic factor for . J Neurosurg.115: 754–759. https://doi.org/10.3171/2011.5.JNS11128

Kim TG, Kim CH, Park JS et al.(2010) Immunological factors relating to the antitumor effect of temozolamide chemoimmunotherapy in a murine glioma modele. Clinical and vaccine immunology Vol.17(1):143–153. https://doi.org/10.1128/CVI.00292-09

Kleijn A, van den Bossche W ,Haefner, ES, Belcaid Z, Burghoorn-Maas C et al.(2017). The Sequence of Delta24-RGD and TMZ Administration in Malignant Glioma Affects the Role of CD8+T Cell Anti-tumor Activity. Molecular Therapy Oncolytics, 5, 11–19. http://doi.org/10.1016/j.omto.2017.02.002

Kmiecik J, Poli A et al (2013) Elevated CD3+ and CD8+ tumor-infiltrating immune cells correlate with prolonged survival in glioblastoma patients despite integrated immunosuppressive mechanisms in the tumor microenvironment and at the systemic level. Journal of Neuroimmunology. Volume 264 , Issue 1: 71–83. https://doi.org/10.1016/j.jneuroim.2013.08.013

Lee KS, Lee K et al. (2017) Prognostic relevance of programmed cell death ligand 1 expression in glioblastoma .Journal of Neuro-Oncology 136: 453-461. https://doi.org/10.1007/s11060-017-2675-6

Leenstra S, Das PK, Troost D, de Boer OJ, Bosch DA (1995)Human malignant astrocytes express macrophage phenotype. J Neuroimmunol 56: 17-25

Louis DN, Ohgaki H, Wiestler OD et al (2007) WHO Classification of Tumours of the Central Nervous System. IARC, Lyon

Mostafa H, Pala A et al (2016) Immune phenotypes predict survival in patients with glioblastoma multiforme. Journal of Hematology & Oncology. https://doi.org/10.1186/s13045-016-0272-3

Ostrand-Rosenberg S, Sinha P (2009) Myeloid-derived suppressor cells: linking inflammation and cancer. J. Immunol. 182: 4499–4506. https://doi.org/10.4049/jimmunol.0802740

Ostrom QT, Gittleman H, Liao P, Vecchione-Koval T, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2017) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2010-2014. Neuro-oncology Volume19(5):1–88. https://doi.org/10.1093/neuonc/nox158

Penttila JM, Pyhala R et al. (1998) Expansion of a Novel Pulmonary CD3- CD4+ CD8+ Cell Population in Mice during Chlamydia pneumoniae Infection. Infection and Immunity Vol. 66(7): 3290–3294

Prendergast CT, Anderton SM (2009) Immune cell entry to central nervous system—current understanding and prospective therapeutic targets. Endocr.Metab. Immune Disord. Drug Targets 9: 315–327. https://doi.org/10.2174/187153009789839219

Roggendorf W, Strupp S, Paulus W (1996) Distribution and characterization of microglia/macrophages in human brain tumours. Acta Neuropathol 92: 288-293

Rossi ML, Hughes JT, Esiri MM, Coakham HB, Brownell DB (1987) Immunohistological study of mononuclear cell infiltrate in malignant gliomas. Acta Neuropathol 74:269-277

Strojnik T, Kavalar R, Zajc I et al. (2009) Prognostic impact of CD68 and kallikrein 6 in human glioma. Anticancer research 29: 3269–3280

Utsuki S, Oka H, Suzuki S, Shimizu S, Tanizaki Y, Kondo K, et al (2006) Pathological and clinical features of cystic and noncystic glioblastomas. Brain Tumor Pathol 23:29–34. https://doi.org/10.1007/s10014-006-0195-8

Yang I, Han SJ, Kaur G, Crane C, Parsa AT (2010) The role of microglia in central nervous system immunity and glioma immunology. J. Clin. Neurosci. 17: 6–10. https://doi.org/10.1016/jocn.2009.05.006

Yongli L, Jin Sh et al. (2017) Function of PD-L1 in antitumor immunity of glioma cells.Saudi Journal of Biological Sciences 24: 803–807. https://doi.org/10.1016/j.sjbs.2015.06.025




DOI: http://dx.doi.org/10.5281/zenodo.1484518

Refbacks

  • There are currently no refbacks.




Copyright (c) 2018 © The Author(s) 2018

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Journal of Education, Health and Sport formerly Journal of Health Sciences

Declaration on the original version.

Editors indicates that the main version of the magazine is to issue a "electronic".

The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019.

1223 Journal of Education, Health and Sport eISSN 2391-8306 7

ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

Archives 2011 - 2014

PBN 2011 - 2014

https://pbn.nauka.gov.pl/sedno-webapp/search?search&searchCategory=WORK&filter.inJournal=36616

POL-index 2011 - 2014

https://pbn.nauka.gov.pl/polindex-webapp/browse/journal/journal-32a319c5-a850-4f44-ba70-1418a6087655

BASE 2011 - 2014

https://www.base-search.net/Search/Results?lookfor=Journal+of+Health+Sciences+%28Radom%29&type=all&oaboost=1&ling=1&name=&thes=&refid=dcrespl&newsearch=1

http://elibrary.ru/contents.asp?titleid=37467

http://journal.rsw.edu.pl/index.php/JHS/issue/archive

Indexed in Bases, Bazy indeksacyjne: ERIH Plus, Worldcat, PBN/POL-Index, ICI Journals Master List, Directory of Open Access Journals (DOAJ), ZBD, Ulrich's periodicals, Google Scholar, Polska Bibliografia Lekarska

US NLM = 101679844

101679844 - NLM Catalog Result - NCBI

https://www.ncbi.nlm.nih.gov/nlmcatalog/101679844

Find a library that holds this journal: http://worldcat.org/issn/23918306

Journal Language(s): English 

PBN Poland

https://pbn.nauka.gov.pl/sedno-webapp/journals/49068

POL-index

https://pbn.nauka.gov.pl/polindex-webapp/browse/journal/journal-c39c8169-88d2-45db-9e7f-d948ce9981c4

BASE

https://www.base-search.net/Search/Results?join=AND&bool0[]=AND&lookfor0[]=2391-8306&type0[]=all&page=11&l=pl&oaboost=1&refid=dcpagepl

Redaction, Publisher and Editorial Office

Instytut Kultury Fizycznej Uniwersytet Kazimierza Wielkiego w Bydgoszczy, Institute of Physical Education Kazimierz Wielki University in Bydgoszcz, Poland 85-091 Bydgoszcz ul. Sportowa 2  www.ukw.edu.pl Copyright by Instytut Kultury Fizycznej UKW w Bydgoszczy http://ojs.ukw.edu.pl/index.php/johs  Open Access ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

The journal has been approved for inclusion in ERIH PLUS.

The ERIH PLUS listing of the journal is available at https://dbh.nsd.uib.no/publiseringskanaler/erihplus/periodical/info?id=485984

SIC Science citation index (calculated on the basis of TCI and Page Rank) 0

Russian Impact factor 0.16

Indexed in Index Copernicus Journals Master List.

http://journals.indexcopernicus.com/Journal+of+Education+Health+and+Sport,p24782242,3.html

ICV 2018 = 95.95 ICV 2017 = 91.30 ICV 2016 = 84.69 ICV 2015 = 93.34 ICV 2014 = 89.51 Standardized Value: 8.27 ICV 2013: 7.32 ICV 2012: 6.41 ICV 20115.48

The InfoBase Index IBI Factor for the year 2015 is 3.56 in InfoBase Index.com.

Website: www.infobaseindex.com

Universal Impact Factor 1.78 for year 2012. (http://www.uifactor.org/AppliedJournals.aspx)

Indexed in Polish Scholarly Bibliography (PBN) (PBN Polska Bibliografia Naukowa) (https://pbn.nauka.gov.pl/journals/36616)

is a portal of the Polish Ministry of Science and Higher Education, collecting information on publications of Polish scientists and on Polish and foreign scholarly journals. Polish Scholarly Bibliograhpy is a part of POL-on - System of Information on Higher Education. It is operated by the Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw.

Indexed in Russian Sciences Index Российский индекс научного цитирования (РИНЦ) http://elibrary.ru/contents.asp?titleid=37467

Indexed in Arianta Polish scientific and professional electronic journals Aneta Drabek i Arkadiusz Pulikowski

(http://www1.bg.us.edu.pl/bazy/czasopisma/czasop_full.asp?id=3595)