Tumour cells are thought to avoid being phagocytosed through expression of the 'self' marker CD47, which ligates the macrophage receptor SIRPα. Alvey et al. investigated the potential of SIRPα-inhibited bone marrow-derived macrophages, primed with tumour-targeting antibodies, to clear tumours in vivo. Systemic injection of these macrophages into tumour-bearing mice increased engulfment of tumour cells compared with host tumour-associated macrophages (TAMs), and tumours regressed. However, anti-tumour effects were limited as donor macrophages eventually underwent mechanosensitive-mediated differentiation into non-phagocytic, high-SIRPα TAMs.