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IL-2 And IL-15 Induced NKG2D, CD158a and CD158b Expression on T, NKT- like and NK Cell Lymphocyte Subsets from Regional Lymph Nodes of Melanoma Patients

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Pathology & Oncology Research

Abstract

Regional lymph nodes (LN)s represent important immunological barriers in spreading of malignant tumors. However, they are the most frequent early metastatic site in melanoma. Immunomodulatory agents including cytokines have been included in therapy of melanoma and have shown severe side effects and toxicity. In this sense, there is a growing need for bringing these agents to further in vitro testing that may enlighten aspects of their regional application. Therefore, the aim of this study was to investigate the effect of interleukin (IL)-2 and IL-15, the two cytokines with similar immune-enhancing effects, on the expression of activating NKG2D, inhibitory CD158a and CD158b receptors on CD8+ T, NKT-like and NK cell lymphocyte subsets from regional LNs of melanoma patients. In this study, we showed significant effects of IL-2 and IL-15 cytokine treatments on the expression of activating NKG2D and on inhibitory CD158a and CD158b receptors on lymphocytes, CD8+ T, NKT-like and NK cell lymphocyte subsets originating from regional LNs of melanoma patients. Furthermore, IL-2 and IL-15 by inducing the expression of NKG2D activating receptor on innate and on adaptive lymphocyte subsets and by augmenting NK cell antitumor cytotoxicity that correlated with the cytokine-induced NKG2D expression, increased antitumor potential of immune cells in regional LNs of melanoma patients irrespective of LN involvement. These findings indicate the importance of immune cell population from regional LNs of melanoma patients in the development of immune intervention strategies that may if applied locally increase antitumor potential to the level that controls tumor progressions.

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Acknowledgments

This study was supported by the grants of the Ministry of education, science and technological development of the Republic of Serbia: grant number 41031 and grant number 175056. The authors wish to thank Jasna Popovic Basić for excellent technical assistance and help during this research.

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Authors and Affiliations

  1. Institute of Oncology and Radiology of Serbia, Pasterova 14, Belgrade, 11000, Serbia

    Ana Vuletić, Irena Jovanić, Zorka Milovanović, Srđan Nikolić, Igor Spurnić & Gordana Konjević

  2. Faculty of Medicine, University of Kragujevac, Kragujevac, Serbia

    Vladimir Jurišić

  3. Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Gordana Konjević

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  1. Ana Vuletić
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  2. Irena Jovanić
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Correspondence to Ana Vuletić.

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Vuletić, A., Jovanić, I., Jurišić, V. et al. IL-2 And IL-15 Induced NKG2D, CD158a and CD158b Expression on T, NKT- like and NK Cell Lymphocyte Subsets from Regional Lymph Nodes of Melanoma Patients. Pathol. Oncol. Res. 26, 223–231 (2020). https://doi.org/10.1007/s12253-018-0444-2

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  • DOI: https://doi.org/10.1007/s12253-018-0444-2

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