Oral Presentation The Melbourne Immunotherapy Network Winter Symposium 2019

Dissecting intratumoural T cell heterogeneity using novel mouse models (#24)

Sarah Sharon Gabriel 1 , Axel Kallies 1
  1. University of Melbourne, Melbourne, VIC, Australia

Cytotoxic T cells are a crucial component of a patients’ anti-tumour immune response, but exhaustion limits their protective function. Immunotherapies aimed at reactivating CD8 T cells through checkpoint inhibition, in particular those targeting PD1/PD-L1, have resulted in dramatically improved survival in patients, highlighting the importance of the anti-tumour CD8 T cell response. Tumour-infiltrating CD8 T cells (TILs) constitute a heterogenous population and presence of cells with certain phenotypes had been associated with better outcome. Exhausted TCF1+ stem or memory-like CD8 cells mediate the proliferative burst in response to checkpoint inhibition and higher frequencies of these cells correlates with better outcome of immunotherapy. Similarly, presence of tissue-resident T cells has been linked to better patient survival. However, the study of TIL heterogeneity is hampered severely by the lack of unequivocal markers for identification and targeting of distinct TIL populations within the tumour environment. To overcome this limitation, we have generated new mouse models that allow simultaneous identification of tissue-resident and memory-like T cells based on fluorescent protein expression. In addition, TIL-specific expression of a Cre recombinase allows fate mapping of these cells and targeting molecules of interest specifically within the tumour. Here we present preliminary data describing TIL heterogeneity and function with help of these novel mouse models.