葡萄膜黑色素瘤相关炎症浸润细胞及免疫治疗
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摘要
巨噬细胞、树突状细胞、自然杀伤细胞、淋巴细胞等免疫细胞,以及相关的白细胞介素-10、转化生长因子-β、干扰素-γ等细胞因子,在葡萄膜黑色素瘤中有着重要的作用机制。肿瘤细胞、免疫细胞和细胞因子之间独特的相互作用表明,免疫治疗可能是治疗葡萄膜黑色素瘤的有效方法。分析这三者之间动态关系的研究将不仅有助于理解肿瘤生长和免疫逃避的病理生理机制,而且有助于研究新的治疗方法。本文主要简述了葡萄膜黑色素瘤相关的免疫细胞、细胞因子对肿瘤细胞的作用,并回顾了常见的免疫治疗进展。
Immune cells,such as macrophages,dendritic cells,natural killer cell,and lymphocytes,as well as related cytokines such as IL-10,TGF-β,and IFN-γ,have an important mechanism in uveal melanoma.The unique interaction between tumor cells,immune cells,and cytokines suggests that immunotherapy may be an effective treatment for uveal melanoma.The analysis of their dynamic relationship will not only help to understand the pathophysiology of tumor growth and immune evasion,but also help to design new treatments.This article briefly describes the effects of uveal melanoma-associated immune cells and cytokines on tumor cells,and gives a review on the progress of common immunotherapy.
Immune cells,such as macrophages,dendritic cells,natural killer cell,and lymphocytes,as well as related cytokines such as IL-10,TGF-β,and IFN-γ,have an important mechanism in uveal melanoma.The unique interaction between tumor cells,immune cells,and cytokines suggests that immunotherapy may be an effective treatment for uveal melanoma.The analysis of their dynamic relationship will not only help to understand the pathophysiology of tumor growth and immune evasion,but also help to design new treatments.This article briefly describes the effects of uveal melanoma-associated immune cells and cytokines on tumor cells,and gives a review on the progress of common immunotherapy.
引文
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[14] STEI M M,LOEFFLER K U,KURTS C,et al.Impact of macrophages on tumor growth characteristics in a murine ocular tumor model[J].Exp Eye Res,2016,151:9-18.
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[16] KUMMER M,SCHULER-THURNER B,BARTZ-SCHMIDT K U,BORNFELD N,CURSIEFEN C,FUISTING B,et al.Immunotherapy of uveal melanoma:vaccination against cancer[J].Methods Mol Biol,2017,1499:273 -278.
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[22] THOMSON A W,KNOLLE P A.Antigen-presenting cell function in the tolerogenic liver environment[J].Nat Rev Immunol,2010,10(11):753-766.
[23] CONSTANTINOS R,DIMITRIOS C,ANESTIS M,CHRISTODOULOS E,CHRISTOS D,APOSTOLOS Z.The expression and prognostic impact of immune cytolytic activity-related markers in human malignancies:A comprehensive meta-analysis[J].Front Oncol,2018,8(27):1-18.
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[26] COUPER K N,BLOUNT D G,RILEY E M.IL-10:the master regulator of immunity to infection[J].J Immunol,2008,180(9):5771-5777.
[27] OLIVA M,RULLAN A J,PIULATS J M.Uveal melanoma as a target for immune-therapy[J].Ann Translat Med,2016,4(9):172.
[28] DURGEAU AURéLIE,YASEMIN V,CORGNAC STéPHANIE,FATHIA M C.Recent advances in targeting CD8 T-cell immunity for more effective cancer immunotherapy[J].Front Immuno,2018,9(14):1-14.
[29] SCHUMACHER T N,SCHREIBER R D.Neoantigens in cancer immunotherapy[J].Science,2015,348(6230):69-74.
[30] COULIE P G,VAN DEN EYNDE B J,VAN DER BRUGGEN P,BOON T.Tumour antigens recognized by T lymphocytes:at the core of cancer immunotherapy[J].Nat Rev Cancer,2014,14(2):135-146.
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[32] ROTHERMEL L D,SABESAN A C,STEPHENS D J,CHANDRAN S S,PARIA B C,SRIVASTAVA A K,et al.Identification of an immunogenic subset of metastatic uveal melanoma[J].Clin Cancer Res,2016,22(9):2237-2249.
[33] LIES B,O’NEILL PATRICK K,QUIGLEY K J,et al.BIITE:A tool to determine HLA class Ⅱ epitopes from T cell ELISpot data[J].PLoS Comput Biol,2016,12(3):e1004796.
[34] BRONKHORST I H G,JAGER M J.Inflammation in uveal melanoma[J].Eye,2013,27(2):217-223.
[35] AHRENDS T,SPANJAARD A,PILZECKER B,BABALA N,BOVENS A,XIAO Y,et al.CD4+T cell help confers a cytotoxic T cell effector program including coinhibitory receptor downregulation and increased tissue invasiveness[J].Immunity,2017,47(5):848-861.
[36] QUEZADA S A,PEGGS K S,SIMPSON T R,ALLISON J P.Shifting the equilibrium in cancer immunoediting:from tumor tolerance to eradication[J].Immunol Rev,2011,241(1):104-118.
[37] MOUGIAKAKOS D,JOHANSSON C C,TROCME E,ALL-ERICSSON C,ECONOMOU M A,LARSSON O,et al.Intratumoral forkhead box P3-positive regulatory T cells predict poor survival in cyclooxygenase-2-positive uveal melanoma[J].Cancer,2010,116(9):2224-2233.
[38] GRIVENNIKOV S I,GRETEN F R,KARIN M.Immunity,inflammation,and cancer[J].Cell,2010,140(6):883-899.
[39] MOTZ G T,COUKOS G.Deciphering and reversing tumor immune suppression[J].Immunity,2013,39(1):61-73.
[40] ASCIERTO P A,MARINCOLA F M.What have we learned from cancer immunotherapy in the last 3 years[J]?J Transl Med,2014,12(1):1-11.
[41] SNYDER A,MAKAROV V,MERGHOUB T,YUAN J,ZARETSKY J M,DESRICHARD A,et al.Genetic basis for clinical response to CTLA-4 blockade in melanoma[J].N Engl J Med,2014,371(23):2189-2199.
[42] SHARMA P,ALLISON J P.The future of immune checkpoint therapy[J].Science,2015,348(6230):56-61.
[43] CHA E,KLINGER M,HOU Y,CUMMINGS C,RIBAS A,FAHAM M.Improved survival with T cell clonotype stability after anti-CTLA-4 treatment in cancer patients[J].Sci Transl Med,2014,6(238):238-270.
[44] JOSHUA A M,MONZON J G,MIHALCIOIU C,HOGG D,SMYLIE M,CHENG T.A phase 2 study of tremelimumab in patients with advanced uveal melanoma[J].Melan Res,2015,25(4):342-347.
[45] BLANK C U.The perspective of immunotherapy:new molecules and new mechanisms of action in immune modulation[J].Curr Opin Oncol,2014,26(2):204-214.
[46] HODI F S,O’DAY S J,MCDERMOTT D F,WEBER R W,SOSMAN J A,HAANEN J B,et al.Improved survival with ipilimumab in patients with metastatic melanoma[J].N Engl J Med,2010,363(8):711-723.
[47] ROBERT C,THOMAS L,BONDARENKO I,O’DAY S,WEBER J,GARBE C,et al.Ipilimumab plus dacarbazine for previously untreated metastatic melanoma[J].N Engl J Med,2011,364(26):2517-2526.
[48] KOMATSUBARA K M,CARVAJAL R D.Immunotherapy for the treatment of uveal melanoma:current status and emerging therapies[J].Curr Oncol Rep,2017,19(7):45.
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