Although PDL1-directed immunotherapy has yielded promising results, a majority of cancer patients do not respond. Using cancer cells and mice, Sheng et al. now show that pharmacological or genetic ablation of the histone demethylase, LSD1, stimulates endogenous retrovirus expression and downregulates RNA-induced silencing complex, resulting in enhanced tumour immunogenicity and T cell infiltration. In a mouse melanoma model, LSD1 ablation sensitized resistant tumours to PD1 blockade. Furthermore, analysis of The Cancer Genome Atlas revealed an inverse correlation between LSD1 expression and CD8+ T cell infiltration in various human cancers.