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Tumor Immunity

Tumor Immunity. 小组成员 ： 李新秀 方园 梁菊华 武永霞 孙笑天 朱建春 张清华 2007.5. Introduction. Tumor antigen Tumor immune response Mechanism of tumor immune escape Immunotherapy of tumors. Tumor Antigen. the new antigen produced by tumor cells

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Tumor Immunity

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  1. Tumor Immunity 小组成员 ： 李新秀 方园 梁菊华 武永霞 孙笑天 朱建春 张清华 2007.5

  2. Introduction Tumor antigen Tumor immune response Mechanism of tumor immune escape Immunotherapy of tumors

  3. Tumor Antigen • the new antigen produced by tumor cells • cause cell immune response and humoral immune response

  4. Immune response T cell Macrophage NK cell • Cellular immune • Humoral immune

  5. B7 CD28 CTL NK MHC TCR Fas Fas L Tumor antigen CD28 MHC B7 Th Th TCR CK MHC TCR MΦ CD28 B7 CK MΦ

  6. Others: • DC • γδT cell • B1 cell • neutrophil

  7. HI 1. Complement-fixing antibodies bind to the tumor cell membrane and promote attachment create pores in the membrane cell disruption due to the loss of osmotic and biochemical integrity.

  8. 2. ADCC: • Many potential effector cells ,including NK cells ,Macrophages ,granulocytes ,can mediate the lytic event . • More efficient in vitro lytic mechanism requiring fewer antibody molecules per cell to kill.

  9. 3 .Opsonization of Ab to Ag • Immune complex • 5. Interferance of tumor cell adhension

  10. Mechanism of Tumor Immune Escape • ⅠSelf-mutation of tumor cells • Ⅱ Inhibition of tumor cells to the immune system

  11. Ⅰ Self-mutation of tumor cells

  12. Regulation and absence of MHC s α1 α2 s s s α3 s β2m s Absence of β2m gene cause the absence of peptide/heavy chain/ β2m complex • Absence of MHCⅠ molecules (2) Diminution of MHCⅠ molecules

  13. (3) Some nonclassical MHC molecules express upward Such as HLA-E ,HLA-G molecules HLA-E CD94/NKG2A (inhibitoryreceptor) Transduct inhibitory signals HLA-G KIR (killing inhibitory receptor) Inhibit the activity of NK cell and CTL

  14. 2. Changes of tumor antigen • Covering or blocking of tumor antigens on the surface of the tumor cells • Low immunogenicity of tumor antigens and antigenic modulation tumor cell T cell

  15. 3. Abnormal express of other molecules on the surface of the tumor cells • Lack of co-stimulatory molecules • Changes of express level of important adhesion molecules • Block the transduction of apoptosis signals

  16. 第一信号 MHCⅠ TCR CD4+T MHCⅡ 共刺激分子 CD28 肿瘤抗原 共刺激分子 B7 第二信号 第一信号 MHCⅠ TCR MHCⅡ CD4+T 肿瘤抗原 共刺激分子 CD28 共刺激分子（沉默型/低免疫原） B7 第二信号

  17. Ⅱ Inhibition of tumor cells to the immune system

  18. Secrete soluble immune inhibitors • 2.Induce the irresponsibility of tumor infiltration lymphocytes • Induce T cell apoptosis • Induce T cell anergy • 3. Immune stimulation IL-4,IL-10

  19. immunotherapy 1.Operation2.Radiacal therapy3.Chemical therapy4.Biological therapy

  20. Administration of Monoclonal Antibodies

  21. Adoptive (过继性) T-cell therapy the cells transferred capable of persisting in the host to be effective be treated by the transfer of tumor – specific syngeneic T cell require an extended period There is now substantial experience with adoptive T-cell transfer in humans..

  22. Immunization to tumor antigen vaccination Such DC loaded with tumor antigens by a variety of means, including transfection, infection with recombinant viruses, incubation with the tumor protein or peptide, or phagocytosis of apoptotic tumor cells can be inoculated（接种）into the patient to induce responses.

  23. Thank You !

  24. Secrete soluble immune inhibitors • eg: • TGF-β: • Promote ineffective response of Th2 • Inhibit Th1

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