Mechanotransduction-Piloted\nWhole-Cell Vaccines for\nSpatiotemporal Modulation of Postoperative Antitumor Immunity

Whole\ntumor cell vaccines hold promise by presenting a broader\nspectrum of autologous-origin tumor antigens to combat postoperative\nrecurrence and metastasis. However, challenges such as intractable\nadjuvant modification and obscure interactions with antigen-presenting\ncells in the postoperative microenvironment impede their translation\ninto effective personalized immunotherapies. In this study, we propose\ncancer vaccines derived from manganese oxide-immobilized resected\ntumor cells, featuring whole tumor antigens and adjustable stiffness\nto modulate interactions with antigen-presenting cells in the postoperative\nmicroenvironment. These vaccines effectively stimulate dendritic cell\nphagocytosis and function through sequential stiffness-mediated mechanotransduction\nand interferon signaling. We evaluated their efficacy using an orthotopic\ntriple-negative breast cancer mouse model and found that combining\nthe vaccines with radiotherapy effectively inhibits postoperative\ntumor recurrence and metastasis. Our study underscores the potential\nof utilizing mechanotransduced adjuvants alongside directly inactivated\nwhole-cell vaccines as a universal solution for preventing postoperative\ntumor recurrence.