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Immune Monitoring

Ulrich Keilholz Dept. of Medical Oncology Peter Martus Dept. of Biostatistics Charité, CBF, Berlin. Immune Monitoring. T cell-mediated destruction of tumor cells. TCR. MHC I. MHC I. CD8+ T cell tumor cell. Granules with perforin und granzymes.

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Immune Monitoring

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  1. Ulrich Keilholz Dept. of Medical Oncology Peter Martus Dept. of Biostatistics Charité, CBF, Berlin Immune Monitoring

  2. T cell-mediated destruction of tumor cells TCR MHC I MHC I CD8+ T cell tumor cell Granules with perforin und granzymes Cytokine release (IFN-, IL-2)

  3. Classes of Tumor-Antigens Class Example Embryonal proteinsMAGE family Tissue antigens Tyrosinase, Proteinase 3 Splice variants Gnt-V Mutated proteins common mutations ras, bcr-abl, cell cycle proteins individual mutations p53, BRCA Individual protein sequences Immunoglobulin idiotype Viral proteins EBV, HPV Transcription factors WT1

  4. T cell Monitoring

  5. 1st generation T cell assays: bulk assays 51CR release GraB, perforin TCR MHC I MHC II Proliferation

  6. 2nd generation T cell assays: „ex vivo“ quantification ELISPOT GraB, perforin Cytokines Tetramer TCR MHC I ICC

  7. 3rd generation T cell assays: specific T cell functions GraB, perforin CD107 Naive Memory Effector Induction of apoptosis (Annexin, caspases) TCR MHC I Th1/Th2 Cytokine profile TRAIL TRAIL-R Induction of necrosis (vital dye exclusion) FAS-L FAS CFSE T T Migration T

  8. Detailed immune monitoring is essential for cancer vaccine development Detailed immune monitoring of non-vaccine treatments may reveal insight into host defese mechanisms that could subsequently be exploited Role of immune monitoring in H&N cancer

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