IMMUNOLOGICAL PARAMETERS OF GLIOMA PATIENTS DEPENDING ON HERPESVIRUS INFECTION OF TUMOR
Keywords:
brain tumors, herpesvirus, peripheral blood, lymphocytes immunophenotype, circulating immune complexes.Abstract
Summary. Aim: to explore the presence of cytomegalovirus (CMV) and Epstein — Barr virus (EBV) in glial tumors and some immunological parameters of this category
patients depending on the characteristics of viral infection.
Object and methods: 25 biopsies of glial tumors were investigated, 64 serum samples, 63 samples of peripheral blood
(36 — neuro-oncological patients, 20 — patients infected
with CMV or EBV without tumor pathology, 7— donors). A
virus determination was carried out using polymerase chain
reaction (PCR); phenotype of peripheral blood lymphocytes
determined by flow cytofluorometry using appropriate combinations of monoclonal antibodies; and levels of circulating immune complexes (CIC). Results: in tumors’ tissue of
patients with brain gliomas DNA CMV by PCR detected
in 16%, EBV— 44%, CMV + EBV— 8% of the samples.
The persistence of these viruses was determined (in 75% of
cases) in glioma anaplasia III–IV degree. Before surgery
patients showed leukocytosis, reducing the relative amount
of lymphocytes, a tendency to decrease of CD8+ T-lymphocytes, statistically significant changes relative and absolute
number of B-lymphocytes (increase) and CD16+ cells (reduction) and increasing the level of CIC. These changes
were most pronounced in patients infected with herpesvirus tumors. Conclusion: herpesvirus infection associated
mainly with a high degree of anaplasia glial brain tumors,
and with more pronounced changes in immunological parameters that indicate suppression of T-cell level and activation of the immune system humoral immune response.
References
Taha MS, Abdalhamid BA, El-Badawy SA, et al. Expression of cytomegalovirus in glioblastoma multiforme: Myth or reality? Br J Neurosurg 2016; 30 (3): 307–12.
Wakefield A, Pignata A, Ghazi A, et al.Is CMV a target in pediatric glioblastoma? Expression of CMV proteins, pp65 and IE1– 72 and CMV nucleic acids in a cohort of pediatric glioblastoma patients. J Neurooncol 2015; 125 (2): 307–15.
Michaelis M, Doerr HW, Cinatl J. The story of human cytomegalovirus and cancer: increasing evidence and open questions. Neoplasia 2009; 11 (1): 1–9.
Harkins L, Volk AL, Samanta M, et al. Specific localisation
of human cytomegalovirus nucleic acids and proteins in human colorectal cancer. Lancet 2002; 360: 1557–63.
Mitchell DA, Xie W, Schmittling R, et al. Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro Oncol 2008; 10: 10–8.
Sao P, Fonseca RF, Rosas SL, et al.Frequency of Epstein-Barr virus DNA sequences in human gliomas. Med J 2015; 133 (1): 51–4.
Luo MH, Fortunato EA. Long-term infection and shedding of human cytomegalovirus in T98G glioblastoma cells. J Virol 2007; 81: 10424–36.
Cobbs CS, Soroceanu L, Denham S. Modulation of oncogenic phenotype in human glioma cells by cytomegalovirus IE1-mediated mitogenicity. Cancer Res 2008; 68: 724–30.
Maussang D, Verzijl D, van Walsum M, et al. Human cytomegalovirus-encoded chemokine receptor US28 promotes tumorigenesis. Proc Natl Acad Sci USA 2006; 103: 13068–73.
Лисяный НИ, Ключникова АИ, Лисяный АН, Кот ЛА. Изучение инфицированности герпесвирусами (ЦМВ, ВЭБ) различных по природе опухолей головного мозга. Онкология 2016; 18 (2): 118–22.
Soderberg-Naucler C. Does cytomegalovirus play a causative role in the development of various inflammatory diseases and cancer? J Intern Med 2006; 259: 219–46.
Barami K. Oncomodulatory mechanisms of human cytomegalovirus in gliomas. J Clin Neurosci 2010; 17: 819–23.
Dziurzynski K, Wei J, Qiao W, Hatiboglu MA, et al. Glioma-associated cytomegalovirus mediates subversion of the monocyte lineage to a tumor propagating phenotype. Clin Cancer Res 2011; 17: 4642–9.
Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol 2007; 7 (1): 41–51.
Louis DN, Ohgak H, Wiestler OD. WHO classification of tumours of the central nervous system. International Agency for Research on Cancer, Lyon, 2007.
Пинегин БВ, Ярилин АА, Симонов АВ и др. Применение проточной цитометрии для оценки функциональной активности иммунной системы человека. Пособие для врачей. М: Медицина, 2001. 57 с.
Гашкова В, Мате Н. Чехословацкая медицина 1978; 2: 117.
Ye ZP, He HY, Wang H, et al. Glioma-derived ADAM10 induces regulatory B cells to suppress CD8+ T cells. PLoS One 2014; 15: 9.
Zhang Y, Morgan R, Podack ER, Rosenblatt J. B cell regulation of anti-tumor immune response. Immunol Res 2013; 57: 115–24.
Kalejta R. Tegument proteins of human cytomegalovirus. Microbiol Mol Biol Rev 2008; 72: 249–65.
Popkin DP, Watson MA, Karaskov E. Murine cytomegalovirus paralyzes macrophages by blocking IFN gamma-induced promoter assembly. Proc Natl Acad Sci USA 2003; 100: 14309–14.
