医学免疫学课件：IL-33及其对肿瘤的效应

1、IL-33及其对肿瘤的效应报告提纲IL-33IL-33对肿瘤的效应乳腺癌肺癌肠癌前景展望报告提纲IL-33IL-33对肿瘤的效应乳腺癌肺癌肠癌前景展望IL-332005年被证实属于IL-1家族主要表达于上皮细胞、内皮细胞、成纤维细胞、部分免疫细胞等警报素 “Alarmin”主要介导二型免疫反应 IL-1 家族11 成员促炎：IL-1, IL-1, IL-18, IL-33, IL-36, IL-36, IL-36抑炎：IL-1Ra, IL-36Ra, IL-37, and IL-38大多数：2号染色体；IL-33：9号染色体四面体结构核心序列蛋白酶加工增强活性IL-1R家族IL-332005年

2、被证实属于IL-1家族主要表达于上皮细胞、内皮细胞、成纤维细胞、部分免疫细胞等警报素 “Alarmin”主要介导二型免疫反应 IL-33结构2. 调控转录3. 无信号肽1. 细胞因子Liew, F.Y., J.P. Girard and H.R. Turnquist, Interleukin-33 in health and disease. Nat Rev Immunol, 2016. 16(11): p. 676-689.IL-33释放与调控警报素DAMPMartin, N.T. and M.U. Martin, Interleukin 33 is a guardian of barrie

3、rs and a local alarmin. Nat Immunol, 2016. 17(2): p. 122-31.IL-33受体ST2IL-1受体家族IL-1RAcp 共同作用sST2 抑制IL-33与ST2的结合二型免疫反应存在于Th2、ILC2、DC、Treg、Macrophage、MC、basophil、eosinophil等de la Fuente, M., T.T. MacDonald and M.A. Hermoso, The IL-33/ST2 axis: Role in health and disease. Cytokine Growth Factor Rev, 201

4、5. 26(6): p. 615-23.IL-332005年被证实属于IL-1家族主要表达于上皮细胞、内皮细胞、成纤维细胞、部分免疫细胞等警报素 “Alarmin”主要介导二型免疫反应 一/二型免疫反应细胞内感染细胞外感染一型二型IL-33与一型免疫反应CTLTh1NKGao, X., et al., Tumoral expression of IL-33 inhibits tumor growth and modifies the tumor microenvironment through CD8+ T and NK cells. J Immunol, 2015. 194(1): p. 4

5、38-45.Bonilla, W.V., et al., The alarmin interleukin-33 drives protective antiviral CD8(+) T cell responses. Science, 2012. 335(6071): p. 984-9.Claudia Baumann, Weldy V. Bonilla, et al., T-bet and STAT4dependent IL-33 receptor expression directly promotes antiviral Th1 cell responses. PNAS, vol. 112

6、 no. 13, 40564061,doi: 10.1073报告提纲IL-33IL-33对肿瘤的效应乳腺癌肺癌肠癌前景展望IL-33对肿瘤的效应血清中IL-33及相关蛋白水平肿瘤中IL-33及相关蛋白水平IL-33对肿瘤的作用可能的机制报告提纲IL-33IL-33对肿瘤的效应乳腺癌肺癌肠癌前景展望乳腺癌血清IL-33水平Jafarzadeh, A., et al., Evaluation of the circulating levels of IL-12 and IL-33 in patients with breast cancer: influences of the tumor sta

7、ges and cytokine gene polymorphisms. Iran J Basic Med Sci, 2015. 18(12): p. 1189-98.乳腺癌血清sST2水平Yang, Z.P., et al., The Association of Serum IL-33 and sST2 with Breast Cancer. Dis Markers, 2015. 2015: p. 516895.IL-33在乳腺癌细胞中的表达Liu, J., et al., Significance of interleukin-33 and its related cytokines i

8、n patients with breast cancers. Front Immunol, 2014. 5: p. 141.IL-33促进乳腺癌生长Milosavljevic, M.Z., et al., Deletion of IL-33R attenuates VEGF expression and enhances necrosis in mammary carcinoma. Oncotarget, 2016. 7(14): p. 18106-15.IL-33促进VEGF产生Milosavljevic, M.Z., et al., Deletion of IL-33R attenuat

9、es VEGF expression and enhances necrosis in mammary carcinoma. Oncotarget, 2016. 7(14): p. 18106-15.血清VEGF水平Yang, Z.P., et al., The Association of Serum IL-33 and sST2 with Breast Cancer. Dis Markers, 2015. 2015: p. 516895IL-33促进乳腺癌的机制损伤IL-33升高 +IL33/ST2 轴转录VEGF免疫调控报告提纲IL-33IL-33对肿瘤的效应乳腺癌肺癌肠癌前景展望非小细

10、胞肺癌 肺癌血清IL-33水平Kim, M.S., et al., Circulating IL-33 level is associated with the progression of lung cancer. Lung Cancer, 2015. 90(2): p. 346-51.肺癌细胞内IL-33水平Akimoto, M., et al., Interleukin-33 enhances programmed oncosis of ST2L-positive low-metastatic cells in the tumour microenvironment of lung ca

11、ncer. Cell Death Dis, 2016. 7: p. e2057.IL-33促进癌症细胞死亡Akimoto, M., et al., Interleukin-33 enhances programmed oncosis of ST2L-positive low-metastatic cells in the tumour microenvironment of lung cancer. Cell Death Dis, 2016. 7: p. e2057.IL-33促进肺癌细胞死亡的机制P38-MAPK、mTOR通路Akimoto, M., et al., Interleukin-

12、33 enhances programmed oncosis of ST2L-positive low-metastatic cells in the tumour microenvironment of lung cancer. Cell Death Dis, 2016. 7: p. e2057.But, IL-33在肺癌中高表达Wang, C., et al., IL-33 signaling fuels outgrowth and metastasis of human lung cancer. Biochem Biophys Res Commun, 2016. 479(3): p. 4

13、61-468IL-33促进肿瘤生长Wang, C., et al., IL-33 signaling fuels outgrowth and metastasis of human lung cancer. Biochem Biophys Res Commun, 2016. 479(3): p. 461-468IL-33促进肿瘤生长的机制Wang, C., et al., IL-33 signaling fuels outgrowth and metastasis of human lung cancer. Biochem Biophys Res Commun, 2016. 479(3): p

14、. 461-468报告提纲IL-33IL-33对肿瘤的效应乳腺癌肺癌肠癌前景展望肿瘤细胞内的IL-33Islam, M.S., et al., Epidermal growth factor is a critical regulator of the cytokine IL-33 in intestinal epithelial cells. Br J Pharmacol, 2016. 173(16): p. 2532-42.肿瘤组织内的ST2Mertz, K.D., et al., The IL-33/ST2 pathway contributes to intestinal tumori

15、genesis in humans and mice. Oncoimmunology, 2016. 5(1): p. e1062966.Cui, G., et al., Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer. Cancer Immunol Immunother, 2015. 64(2): p. 181-90.IL-33/ST2促进肿瘤侵袭Liu, X., et al., IL-33/ST2 pathway con

16、tributes to metastasis of human colorectal cancer. Biochem Biophys Res Commun, 2014. 453(3): p. 486-92.IL-33促进结肠癌肝转移Zhang, Y., et al., IL-33 promotes growth and liver metastasis of colorectal cancer in mice by remodeling the tumor microenvironment and inducing angiogenesis. Mol Carcinog, 2017. 56(1)

17、: p. 272-287.IL-33招募淋巴细胞CD11b+ F4/80+ MCCD11b+Gr1+ MDSCZhang, Y., et al., IL-33 promotes growth and liver metastasis of colorectal cancer in mice by remodeling the tumor microenvironment and inducing angiogenesis. Mol Carcinog, 2017. 56(1): p. 272-287.IL-33破坏小肠上皮，高表达IL-6Zhang, Y., et al., IL-33 prom

18、otes growth and liver metastasis of colorectal cancer in mice by remodeling the tumor microenvironment and inducing angiogenesis. Mol Carcinog, 2017. 56(1): p. 272-287.IL-33促进促瘤细胞因子表达Liu, X., et al., IL-33/ST2 pathway contributes to metastasis of human colorectal cancer. Biochem Biophys Res Commun,

19、2014. 453(3): p. 486-92But，IL-33抑制肿瘤生长Malik, A., et al., IL-33 regulates the IgA-microbiota axis to restrain IL-1alpha-dependent colitis and tumorigenesis. J Clin Invest, 2016. 126(12): p. 4469-4481.IL-33通过募集CTL抑制肿瘤生长ODonnell, C., et al., An antitumorigenic role for the IL-33 receptor, ST2L, in colo

20、n cancer. Br J Cancer, 2016. 114(1): p. 37-43.IL-33对肿瘤的效应促瘤抑瘤Picture：Atlas of Human Anatomy (third addition)报告提纲IL-33IL-33对肿瘤的效应乳腺癌肺癌肠癌前景展望前景展望不“就事论事”挖坑容易填坑难参考文献1.Milosavljevic, M.Z., et al., Deletion of IL-33R attenuates VEGF expression and enhances necrosis in mammary carcinoma. Oncotarget, 2016.

21、7(14): p. 18106-15.2.Martin, N.T. and M.U. Martin, Interleukin 33 is a guardian of barriers and a local alarmin. Nat Immunol, 2016. 17(2): p. 122-31.3.De la Fuente, M., T.T. MacDonald and M.A. Hermoso, The IL-33/ST2 axis: Role in health and disease. Cytokine Growth Factor Rev, 2015. 26(6): p. 615-23

22、.4.Lott, J.M., T.L. Sumpter and H.R. Turnquist, New dog and new tricks: evolving roles for IL-33 in type 2 immunity. J Leukoc Biol, 2015. 97(6): p. 1037-48.5.Hardman, C. and G. Ogg, Interleukin-33, friend and foe in type-2 immune responses. Curr Opin Immunol, 2016. 42: p. 16-24.6.Liew, F.Y., J.P. Gi

23、rard and H.R. Turnquist, Interleukin-33 in health and disease. Nat Rev Immunol, 2016. 16(11): p. 676-689.7.Liew, F.Y., J.P. Girard and H.R. Turnquist, Interleukin-33 in health and disease. Nat Rev Immunol, 2016. 16(11): p. 676-689.8.Gao, X., et al., Tumoral expression of IL-33 inhibits tumor growth

24、and modifies the tumor microenvironment through CD8+ T and NK cells. J Immunol, 2015. 194(1): p. 438-45.9.Milosavljevic, M.Z., et al., Deletion of IL-33R attenuates VEGF expression and enhances necrosis in mammary carcinoma. Oncotarget, 2016. 7(14): p. 18106-15.10.Yang, Z.P., et al., The Association

25、 of Serum IL-33 and sST2 with Breast Cancer. Dis Markers, 2015. 2015: p. 516895.11.Liu, J., et al., Significance of interleukin-33 and its related cytokines in patients with breast cancers. Front Immunol, 2014. 5: p. 141.12.Kim, J.Y., et al., Interleukin-33/ST2 axis promotes epithelial cell transfor

26、mation and breast tumorigenesis via upregulation of COT activity. Oncogene, 2015. 34(38): p. 4928-38.13.Kim, M.S., et al., Circulating IL-33 level is associated with the progression of lung cancer. Lung Cancer, 2015. 90(2): p. 346-51.14.Akimoto, M., et al., Interleukin-33 enhances programmed oncosis

27、 of ST2L-positive low-metastatic cells in the tumour microenvironment of lung cancer. Cell Death Dis, 2016. 7: p. e2057.15.Wang, C., et al., IL-33 signaling fuels outgrowth and metastasis of human lung cancer. Biochem Biophys Res Commun, 2016. 479(3): p. 461-46816.Islam, M.S., et al., Epidermal grow

28、th factor is a critical regulator of the cytokine IL-33 in intestinal epithelial cells. Br J Pharmacol, 2016. 173(16): p. 2532-42.17.Mertz, K.D., et al., The IL-33/ST2 pathway contributes to intestinal tumorigenesis in humans and mice. Oncoimmunology, 2016. 5(1): p. e1062966.18.Cui, G., et al., Dyna

29、mics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer. Cancer Immunol Immunother, 2015. 64(2): p. 181-90.19.Liu, X., et al., IL-33/ST2 pathway contributes to metastasis of human colorectal cancer. Biochem Biophys Res Commun, 2014. 453(3): p. 486-9

30、2.20.Malik, A., et al., IL-33 regulates the IgA-microbiota axis to restrain IL-1alpha-dependent colitis and tumorigenesis. J Clin Invest, 2016. 126(12): p. 4469-4481.21.Tong, X., et al., Interleukin-33 predicts poor prognosis and promotes ovarian cancer cell growth and metastasis through regulating

31、ERK and JNK signaling pathways. Mol Oncol, 2016. 10(1): p. 113-25.22.Gramatzki, D., et al., Interleukin-33 in human gliomas: Expression and prognostic significance. Oncol Lett, 2016. 12(1): p. 445-452.23.Zeng, X., et al., Clinical Significance of Serum Interleukin-31 and Interleukin-33 Levels in Pat

32、ients of Endometrial Cancer: A Case Control Study. Dis Markers, 2016. 2016: p. 9262919.24.Rizner, T.L., Discovery of biomarkers for endometrial cancer: current status and prospects. Expert Rev Mol Diagn, 2016. 16(12): p. 1315-1336.25.Deng, K., et al., Tristetraprolin inhibits gastric cancer progress

33、ion through suppression of IL-33. Sci Rep, 2016. 6: p. 24505.26.Rossle, M., et al., Interleukin-33 Expression Indicates a Favorable Prognosis in Malignant Salivary Gland Tumors. Int J Surg Pathol, 2016. 24(5): p. 394-400.27.Saranchova, I., et al., Discovery of a Metastatic Immune Escape Mechanism In

34、itiated by the Loss of Expression of the Tumour Biomarker Interleukin-33. Sci Rep, 2016. 6: p. 30555.28.Bonilla, W.V., et al., The alarmin interleukin-33 drives protective antiviral CD8(+) T cell responses. Science, 2012. 335(6071): p. 984-9.29.Ye, X.L., et al., IL-33-induced JNK pathway activation

35、confers gastric cancer chemotherapy resistance. Oncol Rep, 2015. 33(6): p. 2746-52.30.Yamada, D., et al., IL-33 facilitates oncogene-induced cholangiocarcinoma in mice by an interleukin-6-sensitive mechanism. Hepatology, 2015. 61(5): p. 1627-42.31.Brunner, S.M., et al., Tumor-infiltrating, interleuk

36、in-33-producing effector-memory CD8(+) T cells in resected hepatocellular carcinoma prolong patient survival. Hepatology, 2015. 61(6): p. 1957-67.32.Chen, R.Y., et al., Effect of oridonin-mediated hallmark changes on inflammatory pathways in human pancreatic cancer (BxPC-3) cells. World J Gastroente

37、rol, 2014. 20(40): p. 14895-903.33.Ishikawa, K., et al., Expression of interleukin-33 is correlated with poor prognosis of patients with squamous cell carcinoma of the tongue. Auris Nasus Larynx, 2014. 41(6): p. 552-7.34.Wang, L., et al., Examining IL-33 expression in the cervix of HPV-infected patients: a preliminary study comparing IL-33 levels in different stages of disease and analyzing its potential association with IFN-gamma. Med Oncol, 2014. 31(9): p. 143.35.Li, J., et al., Biliary repair and carcinogenesis are mediated by IL-33-dependent cholan