Cancer immunotherapy has demonstrated clinical efficacy, exemplified by immune checkpoint blockade; however, immune evasion and poor T-cell infiltration remain major barriers to durable responses. Overcoming these challenges requires coordinated activation of diverse effector cell populations and the establishment of sustained antitumor immunity. To address this, we have developed an artificial adjuvant vector cell (aAVC) platform targeting dendritic cells (DCs), which simultaneously activates innate and adaptive immunity through CD1d-NKT ligand complexes and in vivo delivery of tumor antigens to DCs. In a first-in-human Phase I clinical trial of aAVC-WT1 in relapsed or refractory acute myeloid leukemia, objective leukemic regression was observed and associated with WT1-specific T-cell responses. Paired single-cell RNA and TCR sequencing further identified effector CD8⁺ T-cell clones in the bone marrow. Extending this approach to solid tumors, we analyzed the immune induction process and identified a previously unrecognized spatiotemporal coordination between natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) that drives tumor microenvironment (TME) remodeling in poorly T-cell–infiltrated tumors. Early-infiltrating NK cells establish chemokine-rich niches that promote recruitment of antigen-primed CXCR3+ CTLs and activate myeloid cells and DCs, leading to coordinated structural and inflammatory remodeling of the TME. These interactions are mediated, at least in part, by CCR5–CCL5 and CXCR3–CXCL9 signaling axes. Notably, spatial clustering of NK cells and CTLs at the tumor margin is associated with enhanced cytotoxic activity and sustained immune responses. These findings reveal a fundamental mechanism by which coordinated innate and adaptive immunity converts poorly infiltrated tumors into immune-responsive states.