Core Viewpoint - Immunogenic cell death (ICD) is a promising method for eliciting anti-tumor immune responses, but challenges remain in the spatial and temporal activation of tumor-specific immune responses [1][2]. Group 1: Research Development - A modular metalloprotein in situ vaccine (PPTV) has been developed for cancer immunotherapy, specifically targeting breast cancer [1]. - The research team utilized ferritin as a vaccine framework, integrating optimal mitochondrial-disrupting peptides and loading manganese ions (Mn²⁺) into its core [2]. - A prodrug strategy activated by proteases was developed to address major issues associated with ferritin, such as liver retention and drug leakage [2]. Group 2: Mechanism and Efficacy - In mouse models, PPTV effectively co-delivered mitochondrial-disrupting peptides and Mn²⁺ to tumors, triggering strong anti-tumor immune responses through ICD and the cGAS-STING pathway [2]. - The combination of PPTV with anti-PD-L1 monoclonal antibodies resulted in the eradication of established tumors, highlighting the potential of PPTV as an innovative in situ vaccine platform [2]. Group 3: Clinical Implications - The modular metalloprotein vaccine demonstrates simple preparation and safety features, indicating promising prospects for clinical translation [2].

Core Viewpoint - Immunotherapy, particularly immune checkpoint blockade (ICB), has transformed cancer treatment but remains ineffective in "cold tumors" due to immune suppression in the tumor microenvironment (TME) [2][5][6] Group 1: Research Findings - A new biomimetic Ru/TiO₂ nanobiocatalyst system inspired by natural enzyme reaction systems (ERS) has been developed, capable of rapid, pH-dependent generation of reactive oxygen species (ROS) and oxygen (O₂), effectively converting cold tumors into hot tumors [3][6][7] - The Ru/TiO₂ system enhances anti-tumor immunity and suppresses tumor metastasis when used in conjunction with ICB therapy [3][7] - This research establishes a precedent for adaptive nanobiocatalysts in the TME and paves the way for the development of next-generation immunotherapies targeting drug-resistant cancers [3][6] Group 2: Mechanism of Action - The study demonstrates that Ru/TiO₂ can mediate immunogenic cell death (ICD) in melanoma cells through endoplasmic reticulum stress, while also inhibiting hypoxia-induced immune suppression [7] - The design of Ru/TiO₂ aims to reverse immune suppression and enhance immunogenicity, transforming "immune cold" tumors into "immune hot" tumors [7] Group 3: Clinical Implications - The findings suggest that the rational design of robust and efficient biocatalytic materials could extend beyond cancer treatment, opening new avenues for immune modulation in other diseases [3][6]

Core Viewpoint - The article discusses the development of a biomimetic nanoimmunotherapy that induces PANoptosis to reshape the desmoplastic tumor microenvironment, enhancing anti-tumor immunity and reducing recurrence risk while inhibiting metastasis [3][8]. Group 1: Challenges in Cancer Immunotherapy - Dendritic cell (DC)-based vaccines face significant challenges in solid tumors, including the lack of tumor-specific antigens and the immunosuppressive stroma present in these tumors [5][6]. - Traditional DC vaccines have limited clinical success due to issues such as antigen degradation and immune tolerance, prompting the exploration of hybrid cells formed by fusing DCs with tumor cells [5][6]. Group 2: Innovative Approaches - The study introduces a therapeutic nano-vaccine, UCNP@MOF@MI@FM (UMMF), which combines dendritic cell and tumor hybrid cell membranes, co-loaded with MTH1 inhibitors and tetrahydrobiopterin (BH4) [6][7]. - This platform aims to induce immunogenic cell death (ICD) through PANoptosis, enhancing the activation of cytotoxic T lymphocytes (CTLs) and reprogramming the tumor microenvironment [6][7]. Group 3: Key Findings - The biomimetic nano-vaccine triggers reactive oxygen species (ROS)-induced immunogenic PANoptosis in a spatiotemporal manner [8]. - Near-infrared (NIR) light programming therapy is effective in reshaping the immunosuppressive tumor microenvironment [8]. - The synergistic effect of BH4 with the UMMF nano-vaccine can combat immune therapy resistance [8].