Immunity to tumors Experimental evidence for tumor immunity Tumor - - PowerPoint PPT Presentation

immunity to tumors experimental evidence for tumor
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Immunity to tumors Experimental evidence for tumor immunity Tumor - - PowerPoint PPT Presentation

Immunity to tumors Experimental evidence for tumor immunity Tumor antigens - tumor-specific antigens (TSA): products of mutated genes, can be recognized by both CD4 and CD8 T lymphocytes - tumor-associated antigens (TAA): self proteins,


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Immunity to tumors

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SLIDE 2

Experimental evidence for tumor immunity

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Tumor antigens

  • tumor-specific antigens (TSA): products of mutated genes, can be

recognized by both CD4 and CD8 T lymphocytes

  • tumor-associated antigens (TAA): self proteins, normally expressed at

undetectable levels, overexpressed in tumors - oncofetal antigens, normally expressed during fetal life (e.g. CEA, AFP)

  • viral proteins from oncogenic viruses
  • overexpressed glycolipids (e.g. GM2, GD3)
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Types of tumor antigens recognized by T cells

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Identification of tumor antigens

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Identification of tumor antigens

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Cells involved in anti-tumor responses

Innate immunity

  • NK cells (low MHC, NKG2D→MICA, CD16, IL-2, IL-12→LAK)
  • macrophages (IFNγ→TNF)

Adoptive immunity

  • CTL (cross-priming)
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SLIDE 8

Induction of tumor-specific CTLs

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SLIDE 9

Tumor escape

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Tumor escape

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Tumor escape, tumor editing

  • tumor antigens can induce tolerance (absence of co-stimulation)
  • production of TGFβ → activation of Treg → IL-10, suppression
  • antigen loss→ no recognition
  • MHC loss→ no recognition
  • FasL expression→killing of attacking CTL
  • blockade of the apoptotic machinery
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SLIDE 12

Tumor antigens as vaccines

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Tumor antigens as vaccines

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Tumor cells as vaccines and immunostimulators

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Cytokine-transfected tumor cells as immunotherapy

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Systemic anti-tumor cytokine therapy

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FDA-approved anti-tumor mAbs for therapy

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SLIDE 18

Adoptive cellular therapy

LAK (lymphokine-activated killers)

LAK