An NIR-II-Traceable Nanovaccine Programs Systemic Antigen Residence to Establish Checkpoint-Responsive Progenitor-Exhausted CD8-Positive T‑Cell Reservoirs for Effective Cancer Immunotherapy

This material residence profile enhances antigen uptake, dendritic cell maturation, and stem-like CD8⁺ T-cell generation. NIRVax also accumulates at bone-associated sites, where it is associated with hematopoietic remodeling, myeloid-biased differentiation, and a reduced suppressive myeloid output. Functionally, systemic NIRVax vaccination establishes antigen-specific progenitor-exhausted CD8⁺ T-cell (T_PEX) reservoirs across lymphoid tissues and the tumor microenvironment (TME).

Upon programmed death-ligand 1 (PD-L1) blockade, these reservoirs are mobilized into effector CD8⁺ T-cell responses, leading to tumor immune remodeling, epitope spreading, and improved melanoma control. These findings establish spatiotemporal antigen residence as an engineerable biomaterial parameter for shaping the CD8⁺ T-cell fate and provide a NIR-II-traceable nanovaccine strategy for potentiating checkpoint cancer immunotherapy.