medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2021-10-47-52medalphabet-2063Research ArticleДИАГНОСТИКА И ОНКОТЕРАПИЯDIAGNOSTICS AND ONCOTHERAPYРоль воспаления и провоспалительного цитокина IL-1β в патогенезе и метастазировании рака легких (обзор)Role of inflammation and pro-inflammatory cytokine IL-1β in pathogenesis and metastasis of lung cancer (review)https://orcid.org/0000-0001-7728-9533АртамоноваЕ. В.ArtamonovaE. V.

Артамонова Елена Владимировна, д.м.н., зав. химиотерапевтическим отделением № 1; проф. кафедры

Artamonova Elena V., DM Sci, head of Chemotherapy Dept No. 1; prof. at Oncology and Radiotherapy Dept

Moscow

https://orcid.org/0000-0002-5749-9864ЛактионоваЛ. В.LaktionovaL. V.

Лактионова Людмила Валентиновна – д. м. н., проф. кафедры; зам. генерального директора по медицинской части

 

 

Laktionova Lyudmila V., DM Sci, Prof. department; deputy. General Director for Medical Affairs

Moscow

ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н. Н. Блохина» Минздрава России; ФГAOУ ВО «Российский национальный исследовательский медицинский университет имени И. И. Пирогова»РоссияNational Medical Research Centre of Oncology n.a. N. N. Blokhin; Russian National Research Medical University n.a. N. I. PirogovRussian FederationФГБУ «Национальный медицинский исследовательский центр онкологии имени Н. Н. Блохина» Минздрава России; ЗАО «Медицинский центр в Коломенском»РоссияNational Medical Research Centre of Oncology n.a. N. N. Blokhin; Medical Center in KolomenskoyeRussian Federation202128062021010«Диагностика и онкотерапия» (1)4752Copyright © Артамонова Е.В., Лактионова Л.В., 20212021Артамонова Е.В., Лактионова Л.В.Artamonova E.V., Laktionova L.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/2063

Хроническое воспаление ассоциировано с повышенным риском развития онкологических заболеваний, в том числе рака легкого. Сложное опухолевое микроокружение, формируемое в условиях хронического воспалительного процесса, способствует росту опухоли, инвазии, ангиогенезу и метастазированию. Интерлейкин-1β (IL-1β) – провоспалительный цитокин, играющий важную роль в развитии опухоль- ассоциированного воспаления. Повышенный уровень IL-1β в физиологических жидкостях связан с неблагоприятным прогнозом развития заболевания и инвазивным ростом опухоли. Связывание IL-1β с рецептором и активация сигнальных путей, включая MAPK, COX-2 и Nf-κB, приводят к накоплению в опухолевом микроокружении иммуносупрессорных клеток и выработке медиаторов, способствующих опухолевому росту. Селективное ингибирование IL-1β может повысить эффективность иммунотерапии и химиотерапии путем усиления противоопухолевого иммунного ответа. В данном обзоре рассмотрена роль опухоль-ассоциированного воспаления и IL-1β в патогенезе рака легкого.

Pro-tumor inflammation is associated with increased risk of oncologic malignancies development, including lung cancer. Complex tumor microenvironment which is formed during chronic inflammation contributes to tumor growth, progression, angiogenesis and metastasis. Interleukin-1β (IL-1β) is a cytokine, which plays a key role in pro-tumor inflammation development. Increased level of IL-1β in blood is related to poor prognosis of lung cancer and tumor invasiveness. IL-1β binds to its receptor and activates signaling pathways such as MAPK, COX-2 and Nf-κB, which leads to tumor infiltration with immunosuppressive cells and tumor growth promotion. Selective inhibition of IL-1β can improve the effectiveness of immunotherapy and chemotherapy via enhancing of anti-tumor immunity. In this review we observe a crucial role of pro-tumor inflammation and Il-1β in lung cancer pathogenesis.

опухоль-ассоциированное воспалениеIL-1βопухолевое микроокружениерак легкихpro-tumor inflammationIl-1βtumor microenvironmentlung cancerReferencesGrivennikov S. I., Greten F. R., Karin M. Immunity, inflammation, and cancer. Cell. 2010; 140: 883–899.Grivennikov S. I., Greten F. R., Karin M. Immunity, inflammation, and cancer. Cell. 2010; 140: 883–899.Takahashi H., Ogata H., Nishigaki R., Broide D. H., Karin M. Tobacco smoke promotes lung tumorigenesis by triggering IKKbetaand JNK1-dependent inflammation. Cancer Cell. 2010; 17: 89–97.Takahashi H., Ogata H., Nishigaki R., Broide D. H., Karin M. Tobacco smoke promotes lung tumorigenesis by triggering IKKbetaand JNK1-dependent inflammation. Cancer Cell. 2010; 17: 89–97.O’Callaghan D.S., O’Donnell D., O’Connell F., O’Byrne K. J. The role of inflammation in the pathogenesis of non-small cell lung cancer. J Thorac Oncol. 2010; 5: 2024–2036.O’Callaghan D.S., O’Donnell D., O’Connell F., O’Byrne K. J. The role of inflammation in the pathogenesis of non-small cell lung cancer. J Thorac Oncol. 2010; 5: 2024–2036.Lee J. M., Yanagawa J., Peebles K. A., Sharma S., Mao J. T., Dubinett S. M. Inflammation in lung carcinogenesis: new targets for lung cancer chemoprevention and treatment. Crit. Rev Oncol Hematol. 2008; 66: 208–217.Lee J. M., Yanagawa J., Peebles K. A., Sharma S., Mao J. T., Dubinett S. M. Inflammation in lung carcinogenesis: new targets for lung cancer chemoprevention and treatment. Crit. Rev Oncol Hematol. 2008; 66: 208–217.Mantovani A. et al. Cancer-related inflammation. Nature. 2008; 454: 436–444.Mantovani A. et al. Cancer-related inflammation. Nature. 2008; 454: 436–444.Mantovani A. Cancer: inflaming metastasis. Nature. 2009; 457: 36–37.Mantovani A. Cancer: inflaming metastasis. Nature. 2009; 457: 36–37.Lin W. W., Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J. Clin. Invest. 2007; 117: 1175–1183.Lin W. W., Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J. Clin. Invest. 2007; 117: 1175–1183.Smyth M. J., Dunn G. P. and Schreiber, R. D. Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv. Immunol. 2006; 90: 1–50.Smyth M. J., Dunn G. P. and Schreiber, R. D. Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv. Immunol. 2006; 90: 1–50.Van Gorp H., Lamkanfi M. The emerging roles of inflammasome-dependent cytokines in cancer development. EMBO Rep. 2019; 6: e47575.Van Gorp H., Lamkanfi M. The emerging roles of inflammasome-dependent cytokines in cancer development. EMBO Rep. 2019; 6: e47575.Bunt S. et al. Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression. J Immunol. 2006; 176: 284–290.Bunt S. et al. Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression. J Immunol. 2006; 176: 284–290.Apte R. N. et al. The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions. Cancer Metastasis Rev. 2006; 25: 387–408.Apte R. N. et al. The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions. Cancer Metastasis Rev. 2006; 25: 387–408.O’Donnell JS, Teng MWL, Smyth MJ. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2019; 16 (3): 151–167.O’Donnell JS, Teng MWL, Smyth MJ. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2019; 16 (3): 151–167.Elaraj D. M. et all. The role of interleukin 1 in growth and metastasis of human cancer xenografts. Clin Cancer Res. 2006; 12: 1088–1096.Elaraj D. M. et all. The role of interleukin 1 in growth and metastasis of human cancer xenografts. Clin Cancer Res. 2006; 12: 1088–1096.Apte R. N., Voronov E Is interleukin-1 a good or bad ‘guy’ in tumor immunobiology and immunotherapy? Immunol Rev. 2008; 222: 222–241.Apte R. N., Voronov E Is interleukin-1 a good or bad ‘guy’ in tumor immunobiology and immunotherapy? Immunol Rev. 2008; 222: 222–241.Di Paolo N. C., Shayakhmetov D. M. Interleukin 1α and the inflammatory process. Nat Immunol. 2016; 17: 906–913.Di Paolo N. C., Shayakhmetov D. M. Interleukin 1α and the inflammatory process. Nat Immunol. 2016; 17: 906–913.Bent R., Moll L., Grabbe S., Bros M. Interleukin-1 Beta-A Friend or Foe in Malignancies? Int J Mol Sci. 2018; 19: 2155.Bent R., Moll L., Grabbe S., Bros M. Interleukin-1 Beta-A Friend or Foe in Malignancies? Int J Mol Sci. 2018; 19: 2155.Steel J. L. et al. Prospective analyses of cytokine mediation of sleep and survival in the context of advanced cancer. Psychosom. Med. 2018; 80: 483–491.Steel J. L. et al. Prospective analyses of cytokine mediation of sleep and survival in the context of advanced cancer. Psychosom. Med. 2018; 80: 483–491.Apte R. N. et al. Effects of micro-environmentand malignant cell-derived interleukin-1 in carcinogenesis, tumour invasiveness and tumour-host interactions. Eur. J. Cancer 2006; 42: 751–759.Apte R. N. et al. Effects of micro-environmentand malignant cell-derived interleukin-1 in carcinogenesis, tumour invasiveness and tumour-host interactions. Eur. J. Cancer 2006; 42: 751–759.Gottschlich A., Endres S., Kobold S. Can we use interleukin-1β blockade for lung cancer treatment? Transl Lung Cancer Res. 2018; 7 (Suppl 2): 160–164.Gottschlich A., Endres S., Kobold S. Can we use interleukin-1β blockade for lung cancer treatment? Transl Lung Cancer Res. 2018; 7 (Suppl 2): 160–164.Huang Y., Chen R., Zhou J. E 2FL and NF-kB: Key mediators of inflammation-associated cancers and potential therapeutic targets. Curr. Cancer Drug Targets. 2016; 16: 765–772.Huang Y., Chen R., Zhou J. E 2FL and NF-kB: Key mediators of inflammation-associated cancers and potential therapeutic targets. Curr. Cancer Drug Targets. 2016; 16: 765–772.Kim E. K., Choi E. J. Compromised MAPK signaling in human diseases: An update. Arch. Toxicol. 2015; 89: 867–882.Kim E. K., Choi E. J. Compromised MAPK signaling in human diseases: An update. Arch. Toxicol. 2015; 89: 867–882.Yu H., Pardoll D., and Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat. Rev. Cancer. 2009; 9: 798–809.Yu H., Pardoll D., and Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat. Rev. Cancer. 2009; 9: 798–809.Сandido J., Hagemann T. Cancer-related inflammation. J Clin Immunol. 2013; 33: 79–84.Сandido J., Hagemann T. Cancer-related inflammation. J Clin Immunol. 2013; 33: 79–84.Chen L., Deng H., Cui H., et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018; 9: 7204–7218.Chen L., Deng H., Cui H., et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018; 9: 7204–7218.Mohrherr J., Uras I. Z., Moll H. P., Casanova E. STAT3: versatile functions in non-small cell lung cancer. Cancers 2020; 12 (5): 1017.Mohrherr J., Uras I. Z., Moll H. P., Casanova E. STAT3: versatile functions in non-small cell lung cancer. Cancers 2020; 12 (5): 1017.Gabrilovich D. I., Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009; 9 (3): 162–174.Gabrilovich D. I., Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009; 9 (3): 162–174.Mortaz E., Henricks P. A., Kraneveld A. D., Givi M. E., Garssen J., Folkerts G. Cigarette smoke induces the release of CXCL-8 from human bronchial epithelial cells via TLRs and induction of the inflammasome. Biochim Biophys Acta. 2011; 1812: 1104–1110.Mortaz E., Henricks P. A., Kraneveld A. D., Givi M. E., Garssen J., Folkerts G. Cigarette smoke induces the release of CXCL-8 from human bronchial epithelial cells via TLRs and induction of the inflammasome. Biochim Biophys Acta. 2011; 1812: 1104–1110.Sharma S., Yang S. C., Zhu L. et al. Tumor cyclooxygenase-2/prostaglandin E 2-dependent promotion of FOXP3 expression and CD 4+ CD 25+ T regulatory cell activities in lung cancer. Cancer Res. 2005; 65: 5211–5220.Sharma S., Yang S. C., Zhu L. et al. Tumor cyclooxygenase-2/prostaglandin E 2-dependent promotion of FOXP3 expression and CD 4+ CD 25+ T regulatory cell activities in lung cancer. Cancer Res. 2005; 65: 5211–5220.Sharma S., Stolina M., Yang S. C., et al. Tumor cyclooxygenase 2-dependent suppression of dendritic cell function. Clin Cancer Res. 2003; 9: 961–968.Sharma S., Stolina M., Yang S. C., et al. Tumor cyclooxygenase 2-dependent suppression of dendritic cell function. Clin Cancer Res. 2003; 9: 961–968.Dohadwala M., Batra R. K., Luo J. et al. Autocrine/paracrine prostaglandin E 2 production by non-small cell lung cancer cells regulates matrix metalloproteinase-2 and CD 44 in cyclooxygenase-2-dependent invasion. J Biol Chem. 2002; 277: 50828–50833.Dohadwala M., Batra R. K., Luo J. et al. Autocrine/paracrine prostaglandin E 2 production by non-small cell lung cancer cells regulates matrix metalloproteinase-2 and CD 44 in cyclooxygenase-2-dependent invasion. J Biol Chem. 2002; 277: 50828–50833.Pold M., Zhu L. X., Sharma S et al. Cyclooxygenase-2-dependent expression of angiogenic CXC chemokines ENA-78/CXC Ligand (CXCL) 5 and interleukin-8/CXCL8 in human non-small cell lung cancer. Cancer Res. 2004; 64: 1853–1860.Pold M., Zhu L. X., Sharma S et al. Cyclooxygenase-2-dependent expression of angiogenic CXC chemokines ENA-78/CXC Ligand (CXCL) 5 and interleukin-8/CXCL8 in human non-small cell lung cancer. Cancer Res. 2004; 64: 1853–1860.Castro D., Moreira M., Gouveia A. M., Pozza D. H., De Mello R. A. MicroRNAs in lung cancer. Oncotarget. 2017; 8: 81679–81685.Castro D., Moreira M., Gouveia A. M., Pozza D. H., De Mello R. A. MicroRNAs in lung cancer. Oncotarget. 2017; 8: 81679–81685.Krysan K., Kusko R., Grogan T et al. PGE 2-driven expression of c-Myc and oncomiR-17–92 contributes to apoptosis resistance in NSCLC. Mol Cancer Res. 2014; 12: 765–774.Krysan K., Kusko R., Grogan T et al. PGE 2-driven expression of c-Myc and oncomiR-17–92 contributes to apoptosis resistance in NSCLC. Mol Cancer Res. 2014; 12: 765–774.Voronov E. et all. IL-1 is required for tumor invasiveness and angiogenesis. Proc. Natl. Acad. Sci. 2003; 100: 2645–2650.Voronov E. et all. IL-1 is required for tumor invasiveness and angiogenesis. Proc. Natl. Acad. Sci. 2003; 100: 2645–2650.Lim S. Y., Yuzhalin A. E., Gordon-Weeks A.N., Muschel R. J. Targeting the CCL2-CCR 2 signaling axis in cancer metastasis. Oncotarget 2016; 7: 28697–28710.Lim S. Y., Yuzhalin A. E., Gordon-Weeks A.N., Muschel R. J. Targeting the CCL2-CCR 2 signaling axis in cancer metastasis. Oncotarget 2016; 7: 28697–28710.Slaats J., Ten Oever J., van de Veerdonk F. L., Netea M. G. IL-1b/IL-6/CRP and IL-18/ ferritin: distinct inflammatory programs in infections. PLoS Pathog. 2016; 12: e1005973.Slaats J., Ten Oever J., van de Veerdonk F. L., Netea M. G. IL-1b/IL-6/CRP and IL-18/ ferritin: distinct inflammatory programs in infections. PLoS Pathog. 2016; 12: e1005973.Guo B., Fu S., Zhang J., Liu B., Li Z. Targeting inflammasome/IL-1 pathways for cancer immunotherapy. Sci Rep. 2016; 6: 36107.Guo B., Fu S., Zhang J., Liu B., Li Z. Targeting inflammasome/IL-1 pathways for cancer immunotherapy. Sci Rep. 2016; 6: 36107.Corzo CA, et al. Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells. J Immunol. 2009; 182: 5693–570.Corzo CA, et al. Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells. J Immunol. 2009; 182: 5693–570.Solinas G., Germano G., Mantovani A., Allavena P. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol. 2009; 86: 1065–1073.Solinas G., Germano G., Mantovani A., Allavena P. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol. 2009; 86: 1065–1073.Монастырская Е. А., Лямина С. В., Малышев И. Ю. М1 и М2 фенотипы активированных макрофагов и их роль в иммунном ответе и патологии. Патогенез 2008. Т. 6, № 4., С. 31–39.Монастырская Е. А., Лямина С. В., Малышев И. Ю. М1 и М2 фенотипы активированных макрофагов и их роль в иммунном ответе и патологии. Патогенез 2008. Т. 6, № 4., С. 31–39.Mills C. D., Lenz L. L., Harris R. A. A breakthrough: macrophage-directed cancer immunotherapy. Cancer Res. 2016; 76: 513–516.Mills C. D., Lenz L. L., Harris R. A. A breakthrough: macrophage-directed cancer immunotherapy. Cancer Res. 2016; 76: 513–516.Allavena P., Sica A., Solinas G et al. The inflammatory micro-environment in tumor progression: The role of tumor-associated macrophages. Crit Rev Oncol Hematol 2008; 66: 1–9.Allavena P., Sica A., Solinas G et al. The inflammatory micro-environment in tumor progression: The role of tumor-associated macrophages. Crit Rev Oncol Hematol 2008; 66: 1–9.Nam S. J., Go H., Paik J..H, Kim T. M., Heo D. S., Kim C. W., Jeon Y. K. An increase of M2 macrophages predicts poor prognosis in patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. Leuk Lymphoma. 2014; 55: 2466–2476.Nam S. J., Go H., Paik J..H, Kim T. M., Heo D. S., Kim C. W., Jeon Y. K. An increase of M2 macrophages predicts poor prognosis in patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. Leuk Lymphoma. 2014; 55: 2466–2476.Yuan A. et al. Opposite Effects of M1 and M2 Macrophage Subtypes on Lung Cancer Progression. Sci Rep. 2015; 5: 14273.Yuan A. et al. Opposite Effects of M1 and M2 Macrophage Subtypes on Lung Cancer Progression. Sci Rep. 2015; 5: 14273.Suzuki K. et al. Prognostic immune markers in non-small cell lung cancer. Clin Cancer Res. 2011; 17: 5247–5256.Suzuki K. et al. Prognostic immune markers in non-small cell lung cancer. Clin Cancer Res. 2011; 17: 5247–5256.Chen J. J. et al. Tumor-associated macrophages: the double-edged sword in cancer progression. J Clin Oncol. 2005; 23: 953–964.Chen J. J. et al. Tumor-associated macrophages: the double-edged sword in cancer progression. J Clin Oncol. 2005; 23: 953–964.Bates G. J. et al. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 2006; 24: 5373–5380.Bates G. J. et al. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 2006; 24: 5373–5380.Kotsakis A. et al. Prognostic value of circulating regulatory T cell subsets in untreated non-small cell lung cancer patients. Sci Rep. 2016; 6: 39247.Kotsakis A. et al. Prognostic value of circulating regulatory T cell subsets in untreated non-small cell lung cancer patients. Sci Rep. 2016; 6: 39247.Zhou J. et al. Increased intratumoral regulatory T cells are related to intratumoral macrophages and poor prognosis in hepatocellular carcinoma patients. Int J Cancer. 2009; 125 (7): 1640–1648.Zhou J. et al. Increased intratumoral regulatory T cells are related to intratumoral macrophages and poor prognosis in hepatocellular carcinoma patients. Int J Cancer. 2009; 125 (7): 1640–1648.Ostrand-Rosenberg S., Sinha P. Myeloid-derived suppressor cells: Linking inflammation and cancer J. Immunol. 2009; 182: 4499–4506.Ostrand-Rosenberg S., Sinha P. Myeloid-derived suppressor cells: Linking inflammation and cancer J. Immunol. 2009; 182: 4499–4506.Sinha P., Clements V. K., Fulton A. M., Ostrand-Rosenberg S. Prostaglandin E 2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res. 2007; 67: 4507–4513.Sinha P., Clements V. K., Fulton A. M., Ostrand-Rosenberg S. Prostaglandin E 2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res. 2007; 67: 4507–4513.Kaplanov I., et al. Blocking IL-1β reverses the immunosuppression in mouse breast cancer and synergizes with anti–PD-1 for tumor abrogation. Proc Natl Acad Sci USA. 2019; 116: 1361–1369.Kaplanov I., et al. Blocking IL-1β reverses the immunosuppression in mouse breast cancer and synergizes with anti–PD-1 for tumor abrogation. Proc Natl Acad Sci USA. 2019; 116: 1361–1369.Dinarello C. A. Why not treat human cancer with interleukin-1 blockade? Cancer Metastasis Rev. 2010; 29: 317–329.Dinarello C. A. Why not treat human cancer with interleukin-1 blockade? Cancer Metastasis Rev. 2010; 29: 317–329.Carmi Y., Dotan S., Rider P. et al. The role of IL-1beta in the early tumor cell-induced angiogenic response. J Immunol. 2013; 190: 3500–3509.Carmi Y., Dotan S., Rider P. et al. The role of IL-1beta in the early tumor cell-induced angiogenic response. J Immunol. 2013; 190: 3500–3509.Zhang Q., Zhu B., Li Y. Resolution of cancer-promoting inflammation: a new approach for anticancer therapy. Front Immunol. 2017; 8: 71.Zhang Q., Zhu B., Li Y. Resolution of cancer-promoting inflammation: a new approach for anticancer therapy. Front Immunol. 2017; 8: 71.Zong W. X., and Thompson, C. B. Necrotic death as a cell fate. Genes Dev. 2006; 20: 1–15.Zong W. X., and Thompson, C. B. Necrotic death as a cell fate. Genes Dev. 2006; 20: 1–15.Weide C. et al. Myeloid-derived suppressor cells predict survival of patients with advanced melanoma: comparison with regulatory T cells and NY-ESO-1or melan-A-specific T cells. Clin Cancer Res. 2014; 20: 1601–1609.Weide C. et al. Myeloid-derived suppressor cells predict survival of patients with advanced melanoma: comparison with regulatory T cells and NY-ESO-1or melan-A-specific T cells. Clin Cancer Res. 2014; 20: 1601–1609.Bjoern J. et al. Immunological correlates of treatment and response in stage IV malignant melanoma patients treated with Ipilimumab. Oncoimmunology. 2016; 5: e1100788.Bjoern J. et al. Immunological correlates of treatment and response in stage IV malignant melanoma patients treated with Ipilimumab. Oncoimmunology. 2016; 5: e1100788.

The authors declare that there are no conflicts of interest present.