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Catch Me,

宋春艳. 李龙. maker. 郁舒靓. 商亮. 李丽丽. 孙健. If You Can. Catch Me,. --Mechanisms of Tumor Immune Escape. Tumor cell. Terrorists. T cell. soldiers. Items. Covering or blocking of tumor antigens Surface molecules change. Camouflage. Fas/FasL TGF-β, IL-10. Resistance. Immune selection

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Catch Me,

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  1. 宋春艳 李龙 maker 郁舒靓 商亮 李丽丽 孙健 If You Can Catch Me, --Mechanisms of Tumor Immune Escape

  2. Tumor cell Terrorists T cell soldiers

  3. Items Covering or blocking of tumor antigens Surface molecules change Camouflage Fas/FasL TGF-β, IL-10 Resistance Immune selection Immunodeficiency Surviving

  4. Polysaccharide Tumor cell • Camouflage(伪装) • 1 Covering or blocking of tumor antigens on the surface of the tumor cell

  5. 2.Surface molecule of tumor cell change Lack of class I MHC

  6. Mechanism A B C The disorder of Fas expression and function The unusual expression of FasL sFas

  7. Absence of FasR’s expression 1 2 Absence of FasR’s apoptosis function The disorder of Fas expression and function Esophageal carcinoma Liver carcinoma Gastric carcinoma phosphatase-1

  8. Fas and Tumor Immunity Fas ligand expression by a variety of tumor cell lines and primary tumor isolates. Expression of Fas ligand by tumor cells has been suggested as a tumor escape mechanism, how tumor cells kill activated cytotoxic T cells and thus avoid an anti-tumor immune response.

  9. O’Connell found colon carcinoma cells express functional FasL, thus he announced the model “Fas counterattack” in tumor immune escape. Fas counterattack

  10. normal

  11. Abnormal Tumor and activated T cells Two major pathways for CTL: Fas-mediated and perforrin-mediated

  12. Key words to Fas Fas (CD95) belongs to the supperfamily members of tumor necrosis factor ( TNF) and nerve growth factor (NGF) receptor ,which is expressed in many kinds of cells′surface. DEAD DOMAIN: about 70 amino acids in the plasma region

  13. sFas’s mechanism 1 2 3 sFas prevents the apoptosis mediated by FasL and anti-Fas There are some kinds of mRNA variations. Cells synthesize secretory protein(sFas)

  14. sFas and leukemia Thus, the sfas level is stable and high in the leukemia against treatment. In an experience, leukemia patients' sFas level is higher than normal level.

  15. 活化的CD8+ T细胞 Fas死亡相关区 FasL TNF Fas TNFR Dead tumor cell Actived caspase Inactive procaspase 肿瘤细胞 CTL通过FasL-Fas作用诱导细胞凋亡

  16. Secrete immune inhibitors(TGF-β,IL-10) Definition Tumor cells can secrete a variety of inhibitors to help their escape .They areTGF-β(Transforming Growth Factor β) ,IL-10 and VEGF(Vascular Endothelial Growth Factor) principally. This time we mainly introduce the principle of TGF-β. Almost TGF-β mRNA and TGF-β can be detected in all tumor cells.

  17. TGF-β TGF-β1, TGF-β2 ,TGF-β3) The nucleotide sequences are highly homologous. I, II, III-type

  18. Ⅰ.TGF-β can reduce the expression of MHC class II molecule in the tumor cell surface Yi zhang’s research shows that TGF-β1 can significantly inhibit CⅡTA gene’s transcription. Chang discover CⅡTA gene deficient mice’s immune cell surface defect MHC class II antigen . C II TA can control MHC class II antigen expression. TGF-β1 can inhibit C II TA gene transcription leading to reduce MHC class II antigen expression in tumor cells

  19. Ⅱ.TGF-β acts on DC 1 No or low expression of MHCⅡ molecules. 2 No or low expression of co-stimulatory molecules

  20. Allavena’s study IL-10 can reduce the expression of the surface molecules in DC such as MHC-Ⅱ,CD80,CD86 Inhibit the differentiation and maturation of DC

  21. Ⅲ.TGF-β acts on T cell IL-10 inhibit Th2 • Inhibit the proliferation and differentiation of CTL effectively, influencing to the production of relative CTL • Promote Th2 cells to release IL-10 to inhibit the activation of macrophage and function of Th1 cells.

  22. Immune selection in thedevelopment of cancer: no two tumors are alike • Immune selection • Immune escape and unchecked proliferation Initiation, proliferation diversification Microevolution, selection of immune resistance

  23. The mechanisms of tumor cell escape is far complicated. As far as we are concerned, some mechanisms need being studied more, at the same time , a few of mechanisms have synergy（协同作用）。 The study of mechanism of tumor escape exerts some influences in tumor’s occurring and development, increasing immunity state, reversing tumor escape, etc.

  24. Declaration Hand IN Hand Resisting the Carcinoma Altogether!!!

  25. Thank You

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