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The clinical outcomes of programmed cell death protein‐1 (PD‐1)/programmed death ligand‐1 (PD‐L1) blockade are usually limited by the multiple immune evasion mechanism of the tumor, as well as the immune storm caused by "off‐target" effects of the PD‐1/PD‐L1 antibody. Here, a previously unknown strategy is proposed to synergize the "Ca2+ interference" mediated M2‐like tumor‐associated macrophages (TAM) re‐education and Ca2+‐activating locally PD‐L1 depletion for immunotherapy. The authors discover that calcium‐containing nanoparticles can induce significant "Ca2+ interference" effect and simultaneously reset TAM toward the M1 phenotype through activation of multiple inflammation‐related signaling pathways, as well as NLRP3 inflammasomes, and promoting in situ tumor‐associated antigen release. In addition, a circular aptamer‐DNAzyme conjugate (cAD) is designed with a tumor‐targeting ability and its catalytic shear activity can be specifically activated by Ca2+, which reduces potential autoimmune‐like disorders of PD‐L1 antibody. By simply integrating the ultra‐high pH‐sensitive calcium peroxide nanoparticles with cAD into one nanosystem, it is demonstrated that the nanosystem not only arrest primary tumor progression and lung metastasis but also provides a long‐term immunological memory, which can protect against tumor rechallenge. Therefore, this work provides an attractive strategy for boosting tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Radiotherapy is used in the treatment of ≈50% of patients with cancer. However, tumor repopulation is a major cause of treatment failure after radiotherapy. It is observed that apoptotic tumor following ionizing radiation (IR) accelerated the growth of surviving tumor cells. Here a Gasdermin E and Tannic acid‐based nanoassembly (GT) loaded with manganese tetroxide (Mn3O4) (termed as Mn3O4@GT) is developed to suppress tumor repopulation and improve the treatment outcome of radiotherapy. Mn3O4@GT enables an increase in the reactive oxygen species accumulation in tumor cells, enhancing radiotherapy‐mediated tumor killing. What's more, it can hijack activated caspase 3 to induce tumor pyroptosis, reversing apoptosis‐mediated tumor repopulation. In vivo results shows that Mn3O4@GT significantly reduced the IR induced tumor repopulation by 2.7 fold, resulting in 92% complete regression of tumors. In addition, Mn3O4@GT can sensitize tumors to anti‐PD‐L1 therapy by inducing immunogenic pyroptosis with 85% regression of distant tumors. The caspase 3‐hijacking nanosystem holds a great potential for improving the clinical benefits of radiotherapy. [ABSTRACT FROM AUTHOR]

The article titled "Boosting Tumor Immunotherapy by Bioactive Nanoparticles via Ca2+ Interference Mediated TME Reprogramming and Specific PD-L1 Depletion" discusses the use of bioactive nanoparticles to enhance tumor immunotherapy. The authors acknowledge a mistake in the results of HMGB1 in the supporting information of the article but state that this correction does not impact the overall findings and conclusions of the study. The article provides additional information on the identification numbers of the authors. [Extracted from the article]