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Decreased Interferon γ Production in CD3+ and CD3CD56+ Lymphocyte Subsets in Metastatic Regional Lymph Nodes of Melanoma Patients

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Pathology & Oncology Research

Abstract

As lymphogenic dissemination is very common in melanoma, regional lymph nodes (LN)s represent first immunological barriers to tumor invasion and play a complex role in antitumor immune defense. In this sense, their most prominent role is the presentation of tumor-derived antigens to naïve T cells and generation of cell-mediated adaptive immune response. Since tumor micro-environment affects immune cell function in this study we have evaluated the ability of T cells and NK cells in metastatic (involved) and non-metastatic regional LNs to produce interferon γ (IFNγ), a pleiotropic cytokine that regulates adaptive antitumor immune response. Our results show reduced IFNγ production in both T and NK lymphocyte subsets and decreased prevalence of T cells in metastatic regional LNs of melanoma patients. The decrease of IFNγ production in T cells was more pronounced with increased number of involved regional LNs indicating tumor-induced functional impairment of both T and NK cell lymphocyte subsets in involved regional LNs. Therefore, shown low IFNγ production in metastatic LNs may represent an obstacle in adaptive cell-mediated antitumor immune response and hence may enable tumor progression.

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References

  1. Cochran AJ, Huang RR, Lee J, Itakura E, Leong SP, Essner R (2006) Tumour-induced immune modulation of sentinel lymph nodes. Nat Rev Immunol 6:659–670

    Article  CAS  PubMed  Google Scholar 

  2. Seliger B, Ruiz-Cabello F, Garrido F (2008) IFN inducibility of major histocompatibility antigens in tumors. Adv Cancer Res 101:249–276

    Article  CAS  PubMed  Google Scholar 

  3. Zaidi MR, Merlino G (2011) The two faces of interferon-γ in cancer. Clin Cancer Res 17:6118–6124

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Carrega P, Ferlazzo G (2012) Natural killer cell distribution and trafficking in human tissues. Front Immunol 3:347

    Article  PubMed Central  PubMed  Google Scholar 

  5. Martín-Fontecha A, Lanzavecchia A, Sallusto F (2009) Dendritic cell migration to peripheral lymph nodes. Handb Exp Pharmacol 188:31–49

    Article  PubMed  Google Scholar 

  6. Ferlazzo G, Morandi B (2014) Cross-talks between natural killer cells and distinct subsets of dendritic cells. Front Immunol 5:159

    Article  PubMed Central  PubMed  Google Scholar 

  7. Fehniger TA, Cooper MA, Nuovo GJ, Cella M, Facchetti F, Colonna M, Caligiuri MA (2003) CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity. Blood 101:3052–3057

    Article  CAS  PubMed  Google Scholar 

  8. Morandi B, Bougras G, Muller WA, Ferlazzo G, Münz C (2006) NK cells of human secondary lymphoid tissues enhance T cell polarization via IFN-gamma secretion. Eur J Immunol 36:2394–2400

    Article  CAS  PubMed  Google Scholar 

  9. Lucas M, Schachterle W, Oberle K, Aichele P, Diefenbach A (2007) Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity 26:503–517

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Morandi B, Mortara L, Carrega P, Cantoni C, Costa G, Accolla RS, Mingari MC, Ferrini S, Moretta L, Ferlazzo G (2009) NK cells provide helper signal for CD8+ T cells by inducing the expression of membrane-bound IL-15 on DCs. Int Immunol 21:599–606

    Article  CAS  PubMed  Google Scholar 

  11. Jackson A, Warner N (1986) Preparation, staining and analysis by flow cytometry of peripheral blood leukocytes. In: Rose N, Friedman H, Fahey J (eds) Manual of clinical laboratory immunology, 3rd edn. American Society for Microbiology, Washington, pp 226–235

    Google Scholar 

  12. Farzad Z, Cochran AJ, McBride WH, Gray JD, Wong V, Morton L (1990) Lymphocyte subset alterations in nodes regional to human melanoma. Cancer Res 50:3585–35888

    CAS  PubMed  Google Scholar 

  13. Vuletić A, Jurišić V, Jovanić I, Milovanović Z, Nikolić S, Konjević G (2013) Distribution of several activating and inhibitory receptors on CD3(−)CD56(+) NK cells in regional lymph nodes of melanoma patients. J Surg Res 183:860–868

    Article  PubMed  Google Scholar 

  14. Morton BA, Ramey WG, Paderon H, Miller RE (1986) Monoclonal antibody-defined phenotypes of regional lymph node and peripheral blood lymphocyte subpopulations in early breast cancer. Cancer Res 46(4 Pt 2):2121–2126

    CAS  PubMed  Google Scholar 

  15. Nandakumar S, Woolard SN, Yuan D, Rouse BT, Kumaraguru U (2008) Natural killer cells as novel helpers in anti-herpes simplex virus immune response. J Virol 82:10820–10831

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Adam C, King S, Allgeier T, Braumüller H, Lüking C, Mysliwietz J, Kriegeskorte A, Busch DH, Röcken M, Mocikat R (2005) DC-NK cell cross talk as a novel CD4+ T-cell-independent pathway for antitumor CTL induction. Blood 106:338–344

    Article  CAS  PubMed  Google Scholar 

  17. De Maria A, Bozzano F, Cantoni C, Moretta L (2011) Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-gamma on activation. Proc Natl Acad Sci U S A 108:728–732

    Article  PubMed Central  PubMed  Google Scholar 

  18. Carrega P, Bonaccorsi I, Di Carlo E, Morandi B, Paul P, Rizzello V, Cipollone G, Navarra G, Mingari MC, Moretta L, Ferlazzo G (2014) CD56brightperforinlow noncytotoxic human NK cells are abundant in both healthy and neoplastic solid tissues and recirculate to secondary lymphoid organs via afferent lymph. J Immunol 192:3805–3815

    Article  CAS  PubMed  Google Scholar 

  19. Umansky V, Sevko A (2012) Melanoma-induced immunosuppression and its neutralization. Semin Cancer Biol 22:319–326

    Article  CAS  PubMed  Google Scholar 

  20. Talmadge JE (2011) Immune cell infiltration of primary and metastatic lesions: mechanisms and clinical impact. Semin Cancer Biol 21:131–138

    Article  CAS  PubMed  Google Scholar 

  21. Nevala WK, Vachon CM, Leontovich AA, Scott CG, Thompson MA, Markovic SN (2009) Melanoma Study Group of the Mayo Clinic Cancer Center. Evidence of systemic Th2-driven chronic inflammation in patients with metastatic melanoma. Clin Cancer Res 15:1931–1939

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the grants of the Ministry of Science and Technology 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. Special thanks we owe to doctors form the Department of Surgery at the Institute of Oncology and Radiology of Serbia Dr Neven Jokić, Dr Stevan Jokić, Dr Janko Pralica, Dr Zoran Kozomara, Dr Marko Jevrić, Dr Milan Žegarac, Dr Petar Radlović, Dr Milovan Juškić and Dr Predrag Radovanović.

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Correspondence to Ana Vuletić.

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Vuletić, A., Jovanić, I., Jurišić, V. et al. Decreased Interferon γ Production in CD3+ and CD3CD56+ Lymphocyte Subsets in Metastatic Regional Lymph Nodes of Melanoma Patients. Pathol. Oncol. Res. 21, 1109–1114 (2015). https://doi.org/10.1007/s12253-015-9938-3

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  • DOI: https://doi.org/10.1007/s12253-015-9938-3

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