Deregulation of antigen presentation is a common cancer feature that leads to immune escape. A new study reports an approach to reprogramme tumour cells in vivo, enabling them to present antigens, establish systemic immunity and induce tumour regression.

Using adenoviral delivery of the transcription factors PU.1, IRF8 and BATF3, Ascic et al. reprogrammed mouse tumour cells into type 1 conventional dendritic (cDC1)-like cells. In mouse melanoma models, reprogrammed tumour cells presented antigens similar to cDC1s and induced tumour regression. The authors found that reprogrammed tumour cells caused the formation of dense lymphocyte clusters resembling tertiary lymphoid structures, enhanced the infiltration of memory and stem-like T cells, and induced polyclonal cytotoxic and memory T cell responses. Moreover, the researchers showed that using the same transcription factors could induce a cDC1-like phenotype with enhanced immunogenicity in human xenograft models. Finally, several experiments, including in spheroids, revealed that cDC1 reprogramming and cytotoxicity induction within the human tumour microenvironment was unaffected by immunosuppression.