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Immunity to tumors

Immunity to tumors. Silke Appel Broegelmann Research Laboratory The Gade Institute University of Bergen. Overview. Introduction Tumor antigens Immune response Evasion of immune responses Immunotherapy Role of immune system in promoting tumor growth Summary.

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Immunity to tumors

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  1. Immunity to tumors Silke Appel Broegelmann Research Laboratory The Gade Institute University of Bergen

  2. Overview • Introduction • Tumor antigens • Immune response • Evasion of immune responses • Immunotherapy • Role of immune system in promoting tumor growth • Summary

  3. Evidence for tumor immunity • spontaneous regression • regression of metastases after removal of primary tumor • infiltrations of tumors by lymphocytes and macrophages • lymphocyte proliferation in draining lymph nodes • increased cancer risk after immunosuppression and immunodeficiency

  4. Introduction • tumor cells differ from normal cells => recognition as foreign • immune responses fail to prevent tumor growth • external activation of the immune system

  5. Downloaded from: StudentConsult (on 4 April 2008 09:13 PM) © 2005 Elsevier

  6. Introduction • tumor cells differ from normal cells => recognition as foreign • immune responses fail to prevent tumor growth • external activation of the immune system

  7. Introduction • tumor cells differ from normal cells => recognition as foreign • immune responses fail to prevent tumor growth • external activation of the immune system

  8. Downloaded from: StudentConsult (on 4 April 2008 09:13 PM) © 2005 Elsevier

  9. Downloaded from: StudentConsult (on 4 April 2008 09:13 PM) © 2005 Elsevier

  10. Overview • Introduction • Tumor antigens • Immune response • Evasion of immune responses • Immunotherapy • Role of immune system in promoting tumor growth • Summary

  11. Tumor antigens • mutations • abnormal expression • oncogenic viruses • oncofetal antigens • altered surface modifications • tissue specific differentiation antigens

  12. Tumor antigens - Mutations • point-mutations • deletions • translocations • insertions • specific for tumor cells

  13. Figure 14-12

  14. p53 http://en.wikipedia.org/wiki/P53

  15. BCR/ABL http://en.wikipedia.org/wiki/Philadelphia_chromosome

  16. Tumor antigens • mutations • abnormal expression • oncogenic viruses • oncofetal antigens • altered surface modifications • tissue specific differentiation antigens

  17. Figure 14-13

  18. Figure 14-11 part 1 of 2 Origin of tumor antigens

  19. Figure 14-11 part 2 of 2

  20. Overview • Introduction • Tumor antigens • Immune response • Evasion of immune responses • Immunotherapy • Role of immune system in promoting tumor growth • Summary

  21. Immune responses to tumors • innate immune responses • NK cells • macrophages • adaptive immune responses • T cells • antibodies

  22. Downloaded from: StudentConsult (on 4 April 2008 09:13 PM) © 2005 Elsevier

  23. Overview • Introduction • Tumor antigens • Immune response • Evasion of immune responses • Immunotherapy • Role of immune system in promoting tumor growth • Summary

  24. Figure 14-14 part 1 of 2

  25. Figure 14-14 part 2 of 2

  26. Overview • Introduction • Tumor antigens • Immune response • Evasion of immune responses • Immunotherapy • Role of immune system in promoting tumor growth • Summary

  27. Immunotherapy • stimulation of immune response • vaccination with tumor cells • costimulators and cytokines • block inhibitory pathways • nonspecific stimulation of the immune system

  28. Tumor vaccines

  29. Downloaded from: StudentConsult (on 4 April 2008 09:13 PM) © 2005 Elsevier

  30. Figure 14-20 part 1 of 3

  31. Cytokine gene transfection

  32. Downloaded from: StudentConsult (on 4 April 2008 09:13 PM) © 2005 Elsevier

  33. Systemic cytokine therapy

  34. Immunotherapy • passive immunotherapy • adoptive cellular therapy • graft-versus-leukemia • antibodies

  35. Monoclonal antibodies

  36. Figure 14-17

  37. Overview • Introduction • Tumor antigens • Immune response • Evasion of immune responses • Immunotherapy • Role of immune system in promoting tumor growth • Summary

  38. Promoting tumor growth • chronic inflammation as risk factor for cancer • Helicobacter pylori (gastric cancer) • hepatitis B and C (hepatocellular carcinoma)

  39. Summary • tumor antigens are recognized by immune system • CTL against tumor antigens • antibody therapy • immune response mainly mediated by CTL, NK cells and macrophages • immune evasion • immunotherapy aims at activating the patient’s own immune system to fight the tumor

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