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Combined killing of cancer cells and cross presentation of tumor antigen by Vγ9Vδ2 T cells
  1. Gitte Holmen Olofsson1,
  2. Manja Idorn1,
  3. Ramona Schenker2,
  4. Elfriede Nössner2,
  5. Reno Debets3,
  6. Bernhard Moser4,
  7. Özcan Met5 and
  8. Per thor Straten5
  1. Aff1 grid.4973.90000000406467373Centre for Cancer Immune Therapy, Dept. of HematologyCopenhagen University Hospital Herlev Denmark
  2. Aff2 grid.4567.00000 0004 0483 2525Helmholtz Zentrum München, Germany Research Center for Environmental HealthInstitute for Molecular Immunology Münich Germany
  3. Aff3 grid.5645.2000000040459992XLaboratory of Experimental Tumor ImmunologyErasmus MC Cancer Institute Rotterdam Netherlands
  4. Aff4 grid.7372.10000000088091613Department of Infection, Immunity & BiochemistrySchool of Medicine Cardiff UK
  5. Aff5 grid.411900.d0000000406468325Centre for Cancer Immune Therapy (CCIT)Copenhagen University Hospital Herlev Herlev Denmark

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Meeting abstracts

The human Vγ9Vδ2 T cells are a unique T cell type, and recent studies of the biology of Vγ9Vδ2 T cells emphasize the potential exploitation of these cells in immunotherapy of cancer. Vγ9Vδ2 T cells exhibit dual functionality in that they are both antigen presenting cells (APC) and cytotoxic towards cancer cells. We show that Vγ9Vδ2 T cells can kill cancer cell lines from various cancer types such as leukemia, melanoma, prostate-, and breast cancer, with a significantly increased killing upon treatment of the cancer cells with Zoledronic acid. In addition, we show that Vγ9Vδ2 T cells take up tumor antigens gp100 and MART-1 (long peptide and recombinant protein, respectively), and process these antigens for presentation of class I restricted peptides in the context of the HLA-A02.01 molecule, to be recognized by peptide specific cytotoxic CD8 T cells. Moreover, we show that specific inhibition of the proteasome by lactacystin impair recognition by peptide specific CD8 T cells, strongly suggesting proteasome involvement in presentation of the relevant class I restricted peptides. The dual functions; killing and antigen presentation combined with the ease of expanding Vγ9Vδ2 T cells in vitro from peripheral blood lymphocytes to billions of cells, makes Vγ9Vδ2 T cells attractive vehicles for adoptive cell therapy (ACT) in cancer therapy. Thus, Vγ9Vδ2 T cells are broadly tumor specific killers, that concurrently could induce or support tumor specific αβ-T cell responses.