T cells used in immunotherapy treatments can become exhausted by the task of fighting cancer cells or shut down when they enter tumours. However, a set of CRISPR screens allowed researchers to deactivate each gene in the genome, one at a time, in a pool of human T cells and the team found a handful of candidates that could make T cells resistant to key aspects of the immunosuppressive microenvironment often present in tumours. The researchers were particularly intrigued by a gene called RASA2, as it had never been associated with immune cell function before. The team created T cells with the RASA2 gene knocked out. They then subjected these T cells to various “stress tests” by repeatedly exposing them to cancer cells and models of the tumour microenvironment. They compared the performance of these cells to the original therapeutic T cells that still contained a functional RASA2 gene. Long after the original cells had lost their cancer-fighting abilities, the cells with knocked-out RASA2 remained remarkably tireless. The researchers thus made the therapeutic cells more resistant. This discovery could help overcome a major factor limiting the success of these promising therapies in the fight against solid and liquid tumours.