Nanomedicine-driven strategies for CD8⁺ T cell enhancement in Cancer immunotherapy

Immunotherapy has demonstrated remarkable clinical potential in tumor therapies by activating or augmenting the specific antitumor immune response. CD8⁺ T cells, as the key effector cells of adaptive immunity, play a pivotal role in inducing tumor cell apoptosis. Nevertheless, the immunosuppressive tumor microenvironment substantially restricts the proliferation, infiltration, and cytotoxic activity of CD8⁺ T cells. Furthermore, the depletion and functional impairment of CD8⁺ T cells constitute a major barrier to effective immunotherapy. Recent advances in nanomedicine have provided innovative strategies to overcome immunosuppression and CD8⁺ T cell exhaustion, rejuvenating CD8⁺ T cell-mediated antitumor immunity. In this timely review, a brief outline of the historical development of immunotherapy is first provided, together with a comprehensive overview of T cell classification. This review systematically examines five nanomedicine-driven strategies to potentiate CD8⁺ T cell immunity, including metalloimmunology, regulation of receptors, utilization of CAR-T cell, utilization of exosomes, and normalization of the tumor microenvironment (TME). Finally, the primary existing challenges faced by nanomedicine-driven cancer immunotherapy in clinical translation as well as future perspectives are also outlined. This review will provide guidance for developing next-generation nanomaterial-driven CD8⁺ T cell enhancement in cancer immunotherapy.