Dynamics of blood immunological parameters in patients with glial tumors of varying degrees of anaplasia
DOI:
https://doi.org/10.25305/unj.204112Keywords:
glial tumors, degree of anaplasia, lymphocytes, neutrophils, plateletsAbstract
The patients with glial tumors of varying degrees of anaplasia represent an imbalance in the composition of different subpopulations of immune cells, which leads to both specific immunosuppression and stimulation of the tumor process. For a comprehensive clinical assessment of the state of immunity in the blood, it is recommended to determine the ratio of the absolute level of immune cells, which integrally reflects the violation of certain indicators of innate and acquired immunity.
Objective: To determine the relationship between the absolute number of lymphocytes, neutrophils, and platelets in the peripheral blood in glial tumors of varying degrees of anaplasia and at the stages of surgical treatment.
Materials and methods. The case histories of 95 patients with glial tumors before surgery, on the 5th–7th day after surgery and before reoperation were studied. There were 71 patients initially operated for glial tumors of varying degrees of anaplasia, 40 patients with glioblastomas, 15 patients with anaplastic, and 16 patients with diffuse astrocytomas. Twenty-four patients were re-operated. The comparison group (control) consisted of 28 patients with non-cancerous diseases of the CNS. The age of patients with brain tumors and the comparison group ranged from 35 to 65 years. To analyze blood immunologic parameters, hematologic analyzer Mindray 3000 plus was used to identify the absolute number of platelets, neutrophils, and lymphocytes as well as the ratio index of the absolute number of neutrophils to the absolute number of lymphocytes (n/l), the absolute number of platelets to the absolute content of lymphocytes (p/l), the ratio of the absolute number of platelets to the absolute content of neutrophils (p/n).
Results. In malignant glial tumors (glioblastomas and anaplastic astrocytomas), the level of n/l is significantly increased compared to the diffuse astrocytomas, the stimulation of neutrophil production and inhibition of lymphocyte formation are identified.
On the 5th–7th days after surgery, there is no recovery of subpopulations of immune cells in the peripheral blood. The recurrences of glial tumors are accompanied by the imbalance in the structure of immune cells in peripheral blood that does not depend on the degree of tumors anaplasia.
Conclusions. Determining the ratio of the absolute content of immune cells in the peripheral blood can serve as an informative indicator of the direction of disorders in congenital and acquired immune systems, which should be taken into account in the treatment of tumors.
References
1. Zozulya YuA, Rozumenko VD, Glavatskiy AYa. Chapter 9. [Modern possibilities of surgical treatment of brain gliomas]. In: Zozulya YuA, editor. [Brain gliomas. Current state of the problem and ways of further research]. Kiev: LLC “ExpressPolygraph”; 2007 P. 307-382. Russian.
2. Shamaev MI, Nosov AT, Malysheva TA. Chapter 6. [Modern views on the pathomorphology of brain gliomas]. In: Zozulya YuA, editor. [Brain gliomas. Current state of the problem and ways of further research]. Kiev: LLC “ExpressPolygraph”; 2007 P. 173–234. Russian.
3. Melin BS, Barnholtz-Sloan JS, Wrensch MR, Johansen C, Il’yasova D, Kinnersley B, Ostrom QT, Labreche K, Chen Y, Armstrong G, Liu Y, Eckel-Passow JE, Decker PA, Labussière M, Idbaih A, Hoang-Xuan K, Di Stefano AL, Mokhtari K, Delattre JY, Broderick P, Galan P, Gousias K, Schramm J, Schoemaker MJ, Fleming SJ, Herms S, Heilmann S, Nöthen MM, Wichmann HE, Schreiber S, Swerdlow A, Lathrop M, Simon M, Sanson M, Andersson U, Rajaraman P, Chanock S, Linet M, Wang Z, Yeager M; GliomaScan Consortium, Wiencke JK, Hansen H, McCoy L, Rice T, Kosel ML, Sicotte H, Amos CI, Bernstein JL, Davis F, Lachance D, Lau C, Merrell RT, Shildkraut J, Ali-Osman F, Sadetzki S, Scheurer M, Shete S, Lai RK, Claus EB, Olson SH, Jenkins RB, Houlston RS, Bondy ML. Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors. Nat Genet. 2017 May;49(5):789-794. [CrossRef] [PubMed] [PubMed Central]
4. Zagzag D, Salnikow K, Chiriboga L, Yee H, Lan L, Ali MA, Garcia R, Demaria S, Newcomb EW. Downregulation of major histocompatibility complex antigens in invading glioma cells: stealth invasion of the brain. Lab Invest. 2005 Mar;85(3):328-41. [CrossRef] [PubMed]
5. Berghoff AS, Kiesel B, Widhalm G, Rajky O, Ricken G, Wöhrer A, Dieckmann K, Filipits M, Brandstetter A, Weller M, Kurscheid S, Hegi ME, Zielinski CC, Marosi C, Hainfellner JA, Preusser M, Wick W. Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma. Neuro Oncol. 2015 Aug;17(8):1064-75. [CrossRef] [PubMed] [PubMed Central]
6. Nduom EK, Wei J, Yaghi NK, Huang N, Kong LY, Gabrusiewicz K, Ling X, Zhou S, Ivan C, Chen JQ, Burks JK, Fuller GN, Calin GA, Conrad CA, Creasy C, Ritthipichai K, Radvanyi L, Heimberger AB. PD-L1 expression and prognostic impact in glioblastoma. Neuro Oncol. 2016 Feb;18(2):195-205. [CrossRef] [PubMed] [PubMed Central]
7. Glass R, Synowitz M. CNS macrophages and peripheral myeloid cells in brain tumours. Acta Neuropathol. 2014 Sep;128(3):347-62. [CrossRef] [PubMed]
8. Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L, Quail DF, Olson OC, Quick ML, Huse JT, Teijeiro V, Setty M, Leslie CS, Oei Y, Pedraza A, Zhang J, Brennan CW, Sutton JC, Holland EC, Daniel D, Joyce JA. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med. 2013 Oct;19(10):1264-72. [CrossRef] [PubMed] [PubMed Central]
9. Lisianyi NI, Gnedkova IA, Shmeleva AA, Vaslovych VV, Fedirko VO, Lisianyi AN, Gnedkova MA. [Ratios of cells relating to innate and adaptive immune system in secondary (metastatic) and primary glial cerebral tumors]. Oncology. 2019;21(4):316-322. Russian. [CrossRef]
10. Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011 Jul 25;11(8):519-31. [CrossRef] [PubMed]
11. Shen M, Hu P, Donskov F, Wang G, Liu Q, Du J. Tumor-associated neutrophils as a new prognostic factor in cancer: a systematic review and meta-analysis. PLoS One. 2014 Jun 6;9(6):e98259. [CrossRef] [PubMed] [PubMed Central]
12. Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, Leibowitz-Amit R, Sonpavde G, Knox JJ, Tran B, Tannock IF, Amir E. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014 May 29;106(6):dju124. [CrossRef] [PubMed]
13. Galdiero MR, Garlanda C, Jaillon S, Marone G, Mantovani A. Tumor associated macrophages and neutrophils in tumor progression. J Cell Physiol. 2013 Jul;228(7):1404-12. [CrossRef] [PubMed]
14. Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009 Sep 8;16(3):183-94. [CrossRef] [PubMed] [PubMed Central]
15. Atzpodien J, Reitz M. Peripheral blood neutrophils as independent immunologic predictor of response and long-term survival upon immunotherapy in metastatic renal-cell carcinoma. Cancer Biother Radiopharm. 2008 Feb;23(1):129-34. [CrossRef] [PubMed]
16. Bellocq A, Antoine M, Flahault A, Philippe C, Crestani B, Bernaudin JF, Mayaud C, Milleron B, Baud L, Cadranel J. Neutrophil alveolitis in bronchioloalveolar carcinoma: induction by tumor-derived interleukin-8 and relation to clinical outcome. Am J Pathol. 1998 Jan;152(1):83-92. [PubMed] [PubMed Central]
17. Brandau S, Dumitru CA, Lang S. Protumor and antitumor functions of neutrophil granulocytes. Semin Immunopathol. 2013 Mar;35(2):163-76. [CrossRef] [PubMed]
18. Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, Carbone DP, Gabrilovich DI. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol. 2001 Jan 1;166(1):678-89. [CrossRef] [PubMed]
19. Peranzoni E, Zilio S, Marigo I, Dolcetti L, Zanovello P, Mandruzzato S, Bronte V. Myeloid-derived suppressor cell heterogeneity and subset definition. Curr Opin Immunol. 2010 Apr;22(2):238-44. [CrossRef] [PubMed]
20. Mishalian I, Bayuh R, Levy L, Zolotarov L, Michaeli J, Fridlender ZG. Tumor-associated neutrophils (TAN) develop pro-tumorigenic properties during tumor progression. Cancer Immunol Immunother. 2013 Nov;62(11):1745-56. [CrossRef] [PubMed]
21. Fridlender ZG, Albelda SM. Tumor-associated neutrophils: friend or foe? Carcinogenesis. 2012 May;33(5):949-55. [CrossRef] [PubMed]
22. Sionov RV, Fridlender ZG, Granot Z. The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment. Cancer Microenviron. 2015 Dec;8(3):125-58. [CrossRef] [PubMed] [PubMed Central]
23. Li Z, Yang F, Dunn S, Gross AK, Smyth SS. Platelets as immune mediators: their role in host defense responses and sepsis. Thromb Res. 2011 Mar;127(3):184-8. [CrossRef] [PubMed] [PubMed Central]
24. Menter DG, Tucker SC, Kopetz S, Sood AK, Crissman JD, Honn KV. Platelets and cancer: a casual or causal relationship: revisited. Cancer Metastasis Rev. 2014 Mar;33(1):231-69. [CrossRef] [PubMed] [PubMed Central]
25. Connolly GC, Khorana AA, Kuderer NM, Culakova E, Francis CW, Lyman GH. Leukocytosis, thrombosis and early mortality in cancer patients initiating chemotherapy. Thromb Res. 2010 Aug;126(2):113-8. [CrossRef] [PubMed] [PubMed Central]
26. Han S, Liu Y, Li Q, Li Z, Hou H, Wu A. Pre-treatment neutrophil-to-lymphocyte ratio is associated with neutrophil and T-cell infiltration and predicts clinical outcome in patients with glioblastoma. BMC Cancer. 2015 Sep 4;15:617. [CrossRef] [PubMed] [PubMed Central]
27. Auezova R, Ryskeldiev N, Doskaliyev A, Kuanyshev Y, Zhetpisbaev B, Aldiyarova N, Ivanova N, Akshulakov S, Auezova L. Association of preoperative levels of selected blood inflammatory markers with prognosis in gliomas. Onco Targets Ther. 2016 Oct 11;9:6111-6117. [CrossRef] [PubMed] [PubMed Central]
28. Bambury RM, Teo MY, Power DG, Yusuf A, Murray S, Battley JE, Drake C, O’Dea P, Bermingham N, Keohane C, Grossman SA. The association of pre-treatment neutrophil to lymphocyte ratio with overall survival in patients with glioblastoma multiforme. J Neurooncol. 2013 Aug;114(1):149-54. [CrossRef] [PubMed]
29. Louis DN, Perry A, Reifenberger G, Von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016 Jun;131(6):803-20. [CrossRef] [PubMed]
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2020 Mykola I. Lisianyi, Irina A. Gnedkova, Lyudmyla M. Belska, Viktoriya V. Vaslovich
This work is licensed under a Creative Commons Attribution 4.0 International License.
Ukrainian Neurosurgical Journal abides by the CREATIVE COMMONS copyright rights and permissions for open access journals.
Authors, who are published in this Journal, agree to the following conditions:
1. The authors reserve the right to authorship of the work and pass the first publication right of this work to the Journal under the terms of Creative Commons Attribution License, which allows others to freely distribute the published research with the obligatory reference to the authors of the original work and the first publication of the work in this Journal.
2. The authors have the right to conclude separate supplement agreements that relate to non-exclusive work distribution in the form of which it has been published by the Journal (for example, to upload the work to the online storage of the Journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this Journal is included.
