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Immunity to tumors

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Silke Appel

Broegelmann Research Laboratory

The Gade Institute

University of Bergen

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Overview

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

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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

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Introduction

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

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© 2005 Elsevier

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Introduction

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

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Introduction

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

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Overview

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

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Tumor antigens

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

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Tumor antigens - Mutations

  • point-mutations
  • deletions
  • translocations
  • insertions
  • specific for tumor cells

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Figure 14-12

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p53

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

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BCR/ABL

http://en.wikipedia.org/wiki/Philadelphia_chromosome

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Tumor antigens

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

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Figure 14-13

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Figure 14-11 part 1 of 2

Origin of tumor antigens

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Figure 14-11 part 2 of 2

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Overview

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

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Immune responses to tumors

  • innate immune responses
      • NK cells
      • macrophages
  • adaptive immune responses
      • T cells
      • antibodies

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Overview

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

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Figure 14-14 part 1 of 2

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Figure 14-14 part 2 of 2

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Overview

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

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Immunotherapy

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

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Tumor vaccines

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Figure 14-20 part 1 of 3

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Cytokine gene transfection

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Systemic cytokine therapy

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Immunotherapy

  • passive immunotherapy
      • adoptive cellular therapy
      • graft-versus-leukemia
      • antibodies

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Monoclonal antibodies

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Figure 14-17

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Overview

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

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Promoting tumor growth

  • chronic inflammation as risk factor for cancer
        • Helicobacter pylori (gastric cancer)
        • hepatitis B and C (hepatocellular carcinoma)

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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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