Together, with these studies, our results suggest that prolonged exposure to PD-1-blocking antibody enriches for TIM-3 expression in therapeutic antibody-bound T cells specifically in the tumour microenvironment and not systemically; and additional inhibitory signals through TIM-3 can limit tumour-reactive T cell function in anti-PD-1-resistant tumours. This evidence concerns the gene HAVCR2 and neoplasm.