Nanocatalysts as Emerging Immunomodulators for Enhanced Antitumor Immunotherapy

Cancer immunotherapy has emerged as a transformative therapeutic modality by harnessing the host immune system to achieve durable tumor control. However, its clinical efficacy remains limited by inadequate tumor immunogenicity and an immunosuppressive tumor microenvironment (TME). In recent years, nanocatalytic immunotherapy has attracted growing attention to overcome these barriers by exploiting the catalytic activity of nanomaterials to modulate immune responses in situ. Nanocatalysts catalytically convert endogenous tumor-associated substrates into immunostimulatory species, enabling localized induction of immunogenic cell death (ICD), activation of innate immune sensing pathways such as cGAS-STING, and amplification of adaptive antitumor immunity. Moreover, nanocatalysts serve as powerful tools to remodel the immunosuppressive TME by depleting inhibitory metabolites, alleviating hypoxia, reprogramming suppressive immune cell populations, and improving the delivery and efficacy of immune checkpoint inhibitors. Beyond monotherapy, the integration of nanocatalytic platforms with external energy-driven modalities, including photothermal, photodynamic, sonodynamic, radiodynamic, and electrodynamic therapies, further enables synergistic and spatiotemporally controlled immune activation. In this review, we systematically summarize recent advances in nanocatalyst-based cancer immunotherapy, covering the design principles of catalytic nanomaterials, their immunomodulatory mechanisms, representative therapeutic strategies, and emerging combination approaches. Finally, key challenges and future perspectives toward clinical translation are discussed, highlighting the considerable potential of nanocatalytic strategies for next-generation antitumor immunotherapy.