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Background The ability to promote an immunosuppressive microenvironment has been recognized as one of the “next generation” cancer hallmarks, being most apparent in case of HPV-induced carcinogenesis, since it is a prerequisite to the virus persistence and proliferation of keratinocytes expressing H...

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Published in:European journal of cancer supplements 2015-11, Vol.13 (1), p.31-31
Main Authors: Kurmyshkina, O, Belova, L, Kovchur, P, Volkova, T
Format: Article
Language:English
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Summary:Background The ability to promote an immunosuppressive microenvironment has been recognized as one of the “next generation” cancer hallmarks, being most apparent in case of HPV-induced carcinogenesis, since it is a prerequisite to the virus persistence and proliferation of keratinocytes expressing HPV-antigens. With respect to HPV-associated cervical cancer, it is commonly known that initial pre-cancerous intraepithelial lesions frequently undergo reverse development due to effective recognition and eradication by the immunocompetent cells. Both innate (e.g. NK) and adaptive (helper and cytotoxic O-cells) arms of immunity have been implicated in the regression of neoplastic cells, with NK T-cells considering as a connecting link between two branches. Progression of intraepithelial neoplasia leads to the establishment of pre-invasive cancer, which can be regarded as the result of a completed immunoediting of the tumor locus, because further, with 100% probability, it turns into invasive metastatic form. We assumed that the signs of immune activation, on the one hand, and the signs of immunosuppression, on the other hand, despite the locality of pre-invasive cervical cancer, can be found in the circulation and can be relevant to the development of tolerogenic microenvironment. The aim of the present work was to investigate the number of functionally different subpopulations of T- and NK-lymphocytes in the blood of patients with pre-invasive cervical cancer. Material and methods Blood samples were taken from 35 HPV(+) patients diagnosed with cancer in situ. The control group consisted of 30 healthy HPV(−) women with no pathology of the cervix. Lymphocytes were immunophenotyped by MACSQuant flow cytometer. The percentage of the following populations were measured: CD3+CD95+/high, CD3+CD4+, CD3+CD4+CD95+/high, CD3+CD8+, CD3+CD8+CD95+/high, CD4+CD25+, CD4+CD25high, CD4+CD25+CD127dim/neg, CD4+CD25+FoxP3+ (CD4 Tregs), CD8+CD25+, CD8+CD25+CD127dim/neg, CD8+CD25+FoxP3+ (CD8 Tregs), CD3−CD16+, CD3−CD56+, CD3−(CD16±)CD56bright, CD3−CD16+CD56+, CD3−CD16low/negCD56+, CD3−CD16+CD56- (NK subpopulations), CD3+CD56+, CD3+CD16+CD56+ (NK T-lymphocytes). Results Increase in the number of CD4 Tregs that are known to exert immunosuppressive effect was found in cancer patients’ group, namely the increased quantity of cells with CD4+CD25+ (especially, CD4+CD25high fraction), CD4+CD25+CD127dim/neg, or CD4+CD25+FoxP3+ phenotypes was shown. At the same time, the portion of CD4+FoxP3+
ISSN:1359-6349
DOI:10.1016/j.ejcsup.2015.08.055