Ex vivo expansion and hydrogel-mediated in vivo delivery of tissue-resident memory T cells for immunotherapy

Tissue-resident memory T (T RM ) cells preferentially reside in peripheral tissues, serving as key players in tumor immunity and immunotherapy. The lack of effective approaches for expanding T RM cells and delivering these cells in vivo hinders the exploration of T RM cell–mediated cancer immunotherapy. Here, we report a nanoparticle artificial antigen-presenting cell (nano-aAPC) ex vivo expansion approach and an in vivo delivery system for T RM cells. Using the nano-aAPC platform, we expanded functional antigen-specific murine and human T RM -like CD8 + T cells ex vivo. We also developed an injectable macroporous hyaluronic acid (HA) hydrogel to deliver T RM -like cells. T RM -like cells delivered in the optimized HA hydrogel trigger robust local and systemic antitumor immunity and show synergistic effects with anti–PD-1 treatment. Our findings suggest that nano-aAPC–induced T RM -like cells, coupled with a hydrogel delivery system, offer an efficient way to advance the understanding of T RM cell–mediated cancer therapy.