Autologous erythrocyte microparticles drive antitumour T cell immunity via haem-mediated dendritic cell activation

Current vaccine adjuvants, such as aluminum salts and emulsions, are limited by weak induction of cytotoxic T cell immunity and restricted ability to promote T helper type 1 responses, highlighting the need for safer and more effective alternatives. Here we show that microparticles generated from erythrocytes by controlled ultraviolet irradiation function as potent T helper type 1-skewing adjuvants that enhance tumour antigen-specific cytotoxic T cell responses in vitro and in multiple mouse tumour models. Following uptake by dendritic cells, these microparticles traffic to lysosomes and deliver haem cargo that is subsequently transported to the nucleus. Mechanistically, the particles elevate lysosomal pH, promoting lysosome movement towards the nucleus and enabling haem transfer, where haem activates REV-ERB⍺ and forms a co-repressor complex that suppresses peroxisome proliferator-activated receptor gamma, thereby relieving inhibition of dendritic cell maturation and antigen presentation. In vaccination settings, combining tumour antigens with erythrocyte-derived microparticles enhances cytotoxic T cell activation and suppresses tumour growth with minimal toxicity. These findings establish host-derived vesicles as a promising platform for next-generation cancer vaccine adjuvants.