Immunotherapies aimed at alleviating the inhibitory constraints on T cells have revolutionised cancer management. To date, these have focused on the blockade of cell surface checkpoints such as PD-1. However, not all tumours are responsive to PD-1 checkpoint blockade and both primary and adaptive resistance can occur. An alternative approach by which to alleviate the inhibitory constraints on T cells and overcome T cell exhaustion in the tumor microenvironment may be to target protein-tyrosine-phosphatases (PTPs) that antagonise T cell function. Such PTPs might include the closely related SHP-1 and SHP-2 that are thought to mediate PD-1 inhibitory signalling in T cells, or TCPTP (also known as PTPN2), which antagonises T cell receptor and cytokine signalling and whose deletion enhances T cell-mediated immune surveillance and anti-tumor immunity. Our recent studies have identified PTP1B as an intracellular checkpoint that is upregulated in T cells in tumours. We have shown that the increased PTP1B limits T cell expansion and cytotoxicity to contribute to tumour growth. T cell-specific PTP1B deletion increased STAT-5 signalling and this enhanced the antigen-induced expansion and cytotoxicity of CD8+ T cells to suppress tumour growth. The pharmacological inhibition of PTP1B recapitulated the T cell-mediated repression of tumour growth and enhanced the response to PD-1 blockade. Our findings have identified PTP1B as an intracellular checkpoint whose inhibition can alleviate the inhibitory constraints on T cells to combat cancer.