Given the general downregulation of CD226 expression in the tumour microenvironment due to the presence of immunosuppressive factors, such as TGF-β and hypoxia51,52 our data showing that TIGIT can inhibit TCR signalling independently of CD226 widens the potential value in application of TIGIT blockade as an immunotherapeutic strategy, compared to a model in which co-expression is required. Here, CD226 is linked to neoplasm.