The immense power of the immune system is harnessed in healthy individuals by a range of negative
regulatory signals and checkpoints. Manipulating these checkpoints through inhibition has resulted in
striking immune-mediated clearance of otherwise untreatable tumours and metastases; unfortunately,
not all patients respond to treatment with the currently available inhibitors of cytotoxic T-lymphocyteassociated
protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Combinatorial studies using
both anti-CTLA-4 and anti-PD-1 demonstrate synergistic effects of targeting multiple checkpoints, paving
the way for other immune checkpoints to be targeted. Src homology 2 domain-containing protein tyrosine
phosphatase 1 (SHP-1) is a widely expressed inhibitory protein tyrosine phosphatase (PTP). In T-cells, it
is a negative regulator of antigen-dependent activation and proliferation. It is a cytosolic protein, and
therefore not amenable to antibody-mediated therapies, but its role in activation and proliferation makes
it an attractive target for genetic manipulation in adoptive transfer strategies, such as chimeric antigen
receptor (CAR) T-cells. This review will discuss the potential value of SHP-1 inhibition in future tumour
immunotherapy
