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Autophagy, a lysosome‐involved degradation pathway, as a self‐protective cellular process, always weakens the efficiency of tumor therapies. Herein, for the first time, the biodegradable copper (Cu) ions doped layered double hydroxide (Cu‐LDH) nanoparticles are reported for cancer immunotherapy via lysosomal rupture‐mediated "Broken Window Effect". Only injection of Cu‐LDH single therapeutic agent achieves various organelles destruction after lysosomal rupture, as well as the abnormal aggregation of Cu ions in tumor cells for cuproptosis and pyroptosis. More importantly, autophagy inhibition caused by lysosomal rupture improves Cu ions overload‐mediated cuproptosis and pyroptosis by blocking the lysosome‐mediated bulk degradation pathway, leading to good anti‐tumor immune responses and ultimately high‐efficiency tumor growth inhibition. This lysosomal rupture‐mediated "Broken Window Effect" provides a new paradigm for the autophagy enhanced tumor therapy. [ABSTRACT FROM AUTHOR]

Traditionally referred to as "metabolic junk", lactate has now been recognized as essential "energy currency" and crucial "messenger" that contributes to tumor evolution, immunosuppression, etc., thus presenting a promising strategy for antitumor interventions. Similarly, kynurenine (Kyn) also exerts an immunosuppressive function, thereby significantly compromising the effectiveness of immunotherapy. This study proposes and validates a strategy for enhancing immunotherapy through photothermal‐assisted depletion of lactate sustained by cycle‐like O2 supply, with blocking the tryptophan (Trp)/Kyn metabolic pathway. In brief, a nanozyme therapeutic agent (PNDPL) is constructed, which mainly consists of PtBi nanozymes, lactate oxidase (LOX) and the indoleamine 2,3‐dioxygenase (IDO) inhibitor NLG919. The PtBi nanozymes, which exhibit a catalase (CAT)‐like activity, form a positive feedback loop with LOX to consume lactate while self‐supplying O2. Moreover, PtBi nanozymes retain enzyme‐like performance even in a slightly acidic tumor microenvironment. Under 1064 nm irradiation, photothermal therapy (PTT) not only induces tumor cell death but also accelerates lactate exhaustion. Therefore, the combination of lactate depletion‐induced starvation therapy and PTT, along with the blocking of IDO‐mediated immune escape, effectively inhibits tumor growth and reverses immunosuppressive microenvironment, thus preventing tumor metastasis. This study represents the first investigation into the synergistic antitumor effects by lactate metabolism regulation and IDO‐related immunotherapy. [ABSTRACT FROM AUTHOR]

Myeloid‐derived suppressor cells (MDSCs) refer to a group of immature myeloid cells with potent immunosuppressive capacity upon activation by pathological conditions. Because of their potent immunosuppressive ability, MDSCs have garnered extensive attention in the past few years in the fields of oncology, infection, chronic inflammation and autoimmune diseases. Research on MDSCs in liver diseases has gradually increased, and their potential therapeutic roles will be further explored. This review presents a summary of the involvement and the role played by MDSCs in liver diseases, thus identifying their potential targets for the treatment of liver diseases and providing new directions for liver disease‐related research. [ABSTRACT FROM AUTHOR]

Notwithstanding immune checkpoint blocking (ICB) therapy has made eminent clinical breakthroughs, overcoming immunologically "cold" tumors remains challenging. Here, a cascade potentiated nanomodulator AuPtAg‐GOx is engineered for boosting immune responsiveness. Upon 1064 nm laser irradiation, AuPtAg‐mediated mild photothermal therapy (PTT) activates cytotoxic T lymphocytes and reverses the immunogenic "cold" tumor microenvironment. Further, to amplify the thermal sensitivity of tumor cells, glucose oxidase (GOx) is introduced to suppress the production of heat shock proteins, thereby promoting mild photothermal therapy. Complementarily, AuPtAg nanozymes with catalase‐like activity can ameliorate tumor hypoxia, significantly improving the GOx activity. As a result, the combination of AuPtAg‐GOx with self‐augmented photothermal ability and PD‐L1 antibody can further escalate the antitumor efficacy. The AuPtAg‐GOx‐based synergistic starvation therapy, mild PTT, and immunotherapy cascade enhancement therapy strategy can be a favorable tool to effectively kill cancer cells. [ABSTRACT FROM AUTHOR]

The aberrant metabolic activities of tumor cells not only facilitate tumor proliferation but also impair immune cell function and cause an immunosuppressive tumor microenvironment (TME). Thus, reshaping the metabolic TME while activating innate immunity is highly desirable but challenging. Herein, a multifunctional immunomodulator is engineered for near‐infrared light (NIR)‐triggered photodynamic‐metal‐metabolic immunotherapy via the “internal trouble and outside aggression” strategy. Specifically, an endogenous and exogenous stimuli‐responsive nanoagent is prepared consisting of photosensitizer chlorin e6 (Ce6) modified dense silica‐coated rare earth‐doped nanoparticles (ReNPs@SiO2(Ce6)), with in situ grown ZIF‐8 on the surface for loading glucose transporter‐1 (GLUT‐1) inhibitor Fasentin and glutaminase‐1 inhibitor bis‐2‐(5‐phenylacetamido‐1,3,4‐thiadiazol‐2‐yl)ethyl sulfide (BPTES). The as‐obtained final product is denoted as ReSZ(FB). ReSZ(FB) induces‐ mitochondrial damage and releases mitochondrial DNA (mtDNA) via NIR‐mediated PDT. Subsequently, Zn2+ from ZIF‐8 collaborates with mtDNA to activate the cGAS‐STING pathway, initiating a robust tumor‐specific immune response. Concurrently, Fasentin and BPTES triggeres energy deprivation by blocking glucose uptake and inhibiting glutamine decomposition, thereby reprogramming the metabolic TME, and alleviating immunosuppression. Tumor cells are damaged and trapped into “internal trouble” by combining PDT and energy deprivation, while the sharply enhanced immune cell lethality exposes cancer cells to “outside aggression”. Overall, this photodynamic‐metal‐metabolic immunotherapy provides a promising paradigm for cancer therapy. [ABSTRACT FROM AUTHOR]