Unbiased in vivo CRISPR screen to identify novel T-cell immune checkpoints for cancer immunotherapy

T cells are an important component of the immune system and they can attack and kill tumour cells. However, some tumour cells can inactivate T cells by hijacking natural immune checkpoints that prevent the immune system from targeting normal healthy tissue. A blockade of PD-1, an immune checkpoint receptor on the surface of T cells, prevents the tumour from inactivating T-cells, allowing a reduction in tumour burden. Inhibitors of other checkpoints have also been developed with similar outcomes and when other checkpoints are targeted simultaneously with PD-1, treatment efficacy is considerably improved.

We will systematically test all checkpoint inhibitors for reduction of tumour burden in a melanoma mouse model. We will also use genome editing technologies to identify novel immune checkpoints on T-cells.

This work will help identify novel therapeutic targets for cancer treatment.