C型凝集素受体在肿瘤免疫作用中的研究进展
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摘要
C型凝集素受体(CLRs)是一种高表达于树突状细胞(DCs)的模式识别受体(PRRs),它参与了由DCs介导的针对肿瘤的非特异性免疫和特异性免疫。激活表达于DCs上的CLRs可显著提升机体免疫系统对肿瘤细胞的杀伤作用。本文将以CLRs中的Dectin-1和Dectin-2受体为例,对其在肿瘤免疫中发挥的作用及参与此过程的相关信号通路进行综述,并据此初步探讨CLRs未来在肿瘤免疫治疗中可能的应用。
As one of pattern recognition receptors,C-type lectin receptors( CLTs) were found to be highly expressed by dendritic cells( DCs) and play an important role in the non-specific immunity and specific immunity mediated by DCs towards cancer. Stimulating CLTs expressed on DCs will significantly improve the immunity toward tumor cells. In this review we discuss the role CLTs playing in immunotherapy for tumors and relative signaling pathways,then describe how CLTs can be used in future immunotherapy.
As one of pattern recognition receptors,C-type lectin receptors( CLTs) were found to be highly expressed by dendritic cells( DCs) and play an important role in the non-specific immunity and specific immunity mediated by DCs towards cancer. Stimulating CLTs expressed on DCs will significantly improve the immunity toward tumor cells. In this review we discuss the role CLTs playing in immunotherapy for tumors and relative signaling pathways,then describe how CLTs can be used in future immunotherapy.
引文
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[16] Purwar R,Schlapbach C,Xiao S,et al. Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells[J]. Nat Med,2012,18(8):1248-1253.
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[19] Gringhuis SI,den Dunnen J,Litjens M,et al. Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-κB activation through Raf-1 and Syk[J]. Nat Immunol,2009,10(2):203-213.
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[25] Kimura Y,Inoue A,Hangai S,et al. The innate immune receptor dectin-2 mediates the phagocytosis of cancer cells by kupffer cells for the suppression of liver metastasis[J]. Proc Natl Acad Sci,2016,113(49):14097-14102.
[26] Dupaul-Chicoine J,Arabzadeh A,Dagenais M,et al. The Nlrp3inflammasome suppresses colorectal cancer metastatic growth in the liver by promoting natural killer cell tumoricidal activity[J].Immunity,2015,43(4):751-763.
[27] Temizoz B,Kuroda E,Ishii KJ. Vaccine adjuvants as potential cancer immunotherapeutics[J]. Int Immunol,2016,28(7):329-338.
[28] Marshall ASJ,Willment JA,Pyz E,et al. Human MICL(CLEC12A)is differentially glycosylated and is down-regulated following cellular activation[J]. Eur J Immunol,2006,36(8):2159-2169.
[29] Lahoud MH,Ahmet F,Kitsoulis S,et al. Targeting antigen to mouse dendritic cells via Clec9A induces potent CD4 T cell responses biased toward a follicular helper phenotype[J]. J Immunol,2011,187(2):842.
[30] Hutten TJA,Thordardottir S,Fredrix H,et al. CLEC12A-mediated antigen uptake and cross-presentation by human dendritic cell subsets efficiently boost tumor-reactive T cell responses[J]. J Immunol,2016,197(7):2715.
[31] Sancho D,Mour-SáD,Joffre OP,et al. Tumor therapy in mice via antigen targeting to a novel,DC-restricted C-type lectin[J]. J Clin Invest,2008,118(6):2098-2110.
[32] Yan H,Kamiya T,Suabjakyong P,et al. Targeting C-type lectin receptors for cancer immunity[J]. Front Immunol,2015,6(2):408.
[33] Li B,Cai Y,Qi C,et al. Orally administered particulate betaglucan modulates tumor-capturing dendritic cells and improves antitumor T-cell responses in cancer[J]. Clin Cancer Res,2010,16(21):5153-5164.
[34] Chiffoleau E. C-Type lectin-like receptors as emerging orchestrators of sterile inflammation represent potential therapeutic targets[J]. Front Immunol,2018,9:227.
[2] Akira S,Uematsu S,Takeuchi O. Pathogen recognition and innate immunity[J]. Cell,2006,124(4):783-801.
[3] Ariizumi K,Shen GL,Shikano S,et al. Identification of a novel,dendritic cell-associated molecule,dectin-1,by subtractive CDNA cloning[J]. J Biol Chem,2000,275(26):20157-20167.
[4] Meyer-Wentrup F,Benitez-Ribas D,Tacken PJ,et al. Targeting DCIR on human plasmacytoid dendritic cells results in antigen presentation and inhibits IFN-alpha production[J]. Blood,2008,111(8):4245-4253.
[5] Joo H,Upchurch K,Zhang W,et al. Opposing roles of dectin-1expressed on human plasmacytoid dendritic cells and myeloid dendritic cells in Th2 polarization[J]. J Immunol,2015,195(4):1723-1731.
[6] Herre J,Gordon S,Brown GD. Dectin-1 and its role in the recognition ofβ-glucans by macrophages[J]. Mol Immunol,2004,40(12):869-876.
[7] Yokoyama WM,Plougastel BFM. Immune functions encoded by the natural killer gene complex[J]. Nat Rev Immunol,2003,3(4):304-316.
[8] Fernandez NC,Lozier A,Flament C,et al. Dendritic cells directly trigger NK cell functions:cross-talk relevant in innate anti-tumor immune responses in vivo[J]. Nat Med,1999,5(4):405.
[9] del Fresno C,Soulat D,Roth S,et al. Interferon-βproduction via dectin-1-syk-IRF5 signaling in dendritic cells is crucial for immunity to C. albicans[J]. Immunity,2013,38(6):1176-1186.
[10] Chiba S,Ikushima H,Ueki H,et al. Recognition of tumor cells by dectin-1 orchestrates innate immune cells for anti-tumor responses[J]. Elife,2014,3(2):e04177.
[11] Ebihara T,Azuma M,Oshiumi H,et al. Identification of a Poly I:C-inducible membrane protein that participates in dendritic cellmediated natural killer cell activation[J]. J Exp Med,2010,207(12):2675-2687.
[12] Timmerman JM,Levy R. Dendritic cell vaccines for cancer immunotherapy[J]. Annu Rev Med,1999,50(50):507-529.
[13] LeibundGut-Landmann S,Gross O,Robinson MJ,et al. Syk-and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17[J]. Nat Immunol,2007,8(6):630-638.
[14] Nishimura T,Nakui M,Sato M,et al. The critical role of Th1-dominant immunity in tumor immunology[J]. Cancer Chemother Pharmacol,2000,46(1):S52-S61.
[15] Ji Y,Zhang W. Th17 cells:positive or negative role in tumor?[J]. Immunol Immunother,2010,59:979-987.
[16] Purwar R,Schlapbach C,Xiao S,et al. Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells[J]. Nat Med,2012,18(8):1248-1253.
[17] Lu Y,Hong S,Li H,et al. Th9 cells promote antitumor immune responses in vivo[J]. J Clin Invest,2012,122(11):4160-4171.
[18] Zhao Y,Chu X,Chen J,et al. Dectin-1-activated dendritic cells trigger potent antitumour immunity through the induction of Th9cells[J]. Nat Commun,2016,7:12368.
[19] Gringhuis SI,den Dunnen J,Litjens M,et al. Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-κB activation through Raf-1 and Syk[J]. Nat Immunol,2009,10(2):203-213.
[20] Lu Y,Yi Q. Utilizing T9 cells as a novel therapeutic strategy for malignancies[J]. Oncoimmunology,2013,2(3):e23084.
[21] Daley D,Mani VR,Mohan N,et al. Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance[J]. Nat Med,2017,23(5):556-567.
[22] Ariizumi K,Shen GL,Shikano S,et al. Cloning of a second dendritic cell-associated C-type lectin(Dectin-2)and its alternatively spliced isoforms[J]. J Biol Chem,2000,275(16):11957-11963.
[23] Taylor PR,Reid DM,Heinsbroek SEM,et al. Dectin-2 is predominantly myeloid restricted and exhibits unique activationdependent expression on maturing inflammatory monocytes elicited in vivo[J]. Eur J Immunol,2005,35(7):2163-2174.
[24] Sancho D,Reis e Sousa C. Signaling by myeloid C-type lectin receptors in immunity and homeostasis[J]. Annu Rev Immunol,2012,30(1):491.
[25] Kimura Y,Inoue A,Hangai S,et al. The innate immune receptor dectin-2 mediates the phagocytosis of cancer cells by kupffer cells for the suppression of liver metastasis[J]. Proc Natl Acad Sci,2016,113(49):14097-14102.
[26] Dupaul-Chicoine J,Arabzadeh A,Dagenais M,et al. The Nlrp3inflammasome suppresses colorectal cancer metastatic growth in the liver by promoting natural killer cell tumoricidal activity[J].Immunity,2015,43(4):751-763.
[27] Temizoz B,Kuroda E,Ishii KJ. Vaccine adjuvants as potential cancer immunotherapeutics[J]. Int Immunol,2016,28(7):329-338.
[28] Marshall ASJ,Willment JA,Pyz E,et al. Human MICL(CLEC12A)is differentially glycosylated and is down-regulated following cellular activation[J]. Eur J Immunol,2006,36(8):2159-2169.
[29] Lahoud MH,Ahmet F,Kitsoulis S,et al. Targeting antigen to mouse dendritic cells via Clec9A induces potent CD4 T cell responses biased toward a follicular helper phenotype[J]. J Immunol,2011,187(2):842.
[30] Hutten TJA,Thordardottir S,Fredrix H,et al. CLEC12A-mediated antigen uptake and cross-presentation by human dendritic cell subsets efficiently boost tumor-reactive T cell responses[J]. J Immunol,2016,197(7):2715.
[31] Sancho D,Mour-SáD,Joffre OP,et al. Tumor therapy in mice via antigen targeting to a novel,DC-restricted C-type lectin[J]. J Clin Invest,2008,118(6):2098-2110.
[32] Yan H,Kamiya T,Suabjakyong P,et al. Targeting C-type lectin receptors for cancer immunity[J]. Front Immunol,2015,6(2):408.
[33] Li B,Cai Y,Qi C,et al. Orally administered particulate betaglucan modulates tumor-capturing dendritic cells and improves antitumor T-cell responses in cancer[J]. Clin Cancer Res,2010,16(21):5153-5164.
[34] Chiffoleau E. C-Type lectin-like receptors as emerging orchestrators of sterile inflammation represent potential therapeutic targets[J]. Front Immunol,2018,9:227.