Poster Presentation Lorne Infection and Immunity 2020

Success and failure of adoptive T cell therapy against cancer (#120)

Christina Scheffler 1 , Jose Villadangos 1 2 , Justine Mintern 2
  1. Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria, Australia
  2. Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Victoria, Australia

Adoptive T cell therapy (ACT) is a promising immunotherapeutic approach to fight cancer by utilising cytotoxic T lymphocytes (CTL), which specifically target and eradicate tumour cells. However, one major limitation of this therapy is the ability of tumours to interfere with the CTL through immune escape mechanisms. In a mouse model of B-cell lymphoma and ACT, we investigate the mechanisms underlying this failure. We found that tumour-specific CTL fail to eradicate lymphoma cells once the tumour burden reaches a certain threshold. In this case a major proportion of the CTL is rapidly deleted and those remaining lose their effector function, a process we call “stunning”. We investigate the underlying mechanisms of stunning by comparing characteristics of CTL and tumour cells in a small tumour setting, where CTL successfully eradicate tumour cells with a large tumour setting, where stunning occurs.