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Potent STING activation stimulates immunogenic cell death to enhance antitumor immunity in neuroblastoma

Neuroblastoma (NB) is a childhood cancer for which new treatment options are needed. The success of immune checkpoint blockade in the treatment of adult solid tumors has prompted the exploration of immunotherapy in NB; however, clinical evidence indicates that the vast majority of NB patients do...


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Downregulation of RIG-I mediated by ITGB3/c-SRC/STAT3 signaling confers resistance to interferon-α-induced apoptosis in tumor-repopulating cells of melanoma

Interferon-α (IFN-α) plays a pivotal role in host antitumor immunity, and the evasion of IFN-α signaling pathway can lead to IFN-α resistance during the treatment of cancer. Although the interplay between IFN-α and tumor cells has been extensively investigated in differentiated tumor cells, much...


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Novel, genetically induced mouse model that recapitulates the histological morphology and immunosuppressive tumor microenvironment of metastatic peritoneal carcinomatosis

Peritoneal carcinomatosis is a hallmark of advanced peritoneal tumor progression, particularly for tubal/ovarian high-grade serous carcinomas (HGSCs). Patients with peritoneal carcinomatosis have poor survival rates and are difficult to treat clinically due to widespread tumor dissemination in...


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CCL5-armed oncolytic virus augments CCR5-engineered NK cell infiltration and antitumor efficiency

Natural killer (NK) cells have potent antitumor activities. Nevertheless, adoptive transfer therapy of NK cells has gained very limited success in patients with solid tumors as most infused NK cells remain circulating in the peripheral blood instead of entering tumor sites. Chemokines and their...


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Interferon gamma inhibits CXCL8–CXCR2 axis mediated tumor-associated macrophages tumor trafficking and enhances anti-PD1 efficacy in pancreatic cancer

Pancreatic cancer (PC) is a common malignancy of the digestive system and is characterized by poor prognosis and early metastasis. Tumor immune escape plays an important role in PC progression. Programmed death 1 (PD1) blockade therapy is a promising treatment for patients with PC, but is yet to...


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NF-κB p50-deficient immature myeloid cell (p50-IMC) adoptive transfer slows the growth of murine prostate and pancreatic ductal carcinoma

Macrophages and dendritic cells lacking the transcription factor nuclear factor kappa B p50 are skewed toward a proinflammatory phenotype, with increased cytokine expression and enhanced T cell activation; additionally, murine melanoma, fibrosarcoma, colon carcinoma, and glioblastoma grow slower...


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Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody-dependent cell-mediated phagocytosis

The monoclonal antibody (mAb) trastuzumab is part of the standard of care for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer. Antibody-dependent cell-mediated phagocytosis (ADCP) and cytotoxicity (ADCC) are major mechanisms of action of the mAb...


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Blocking CD47 efficiently potentiated therapeutic effects of anti-angiogenic therapy in non-small cell lung cancer

Inhibitors targeting VEGF and VEGFR are commonly used in the clinic, but only a subset of patients could benefit from these inhibitors and the efficacy was limited by multiple relapse mechanisms. In this work, the authors aimed to investigate the role of innate immune response in anti-angiogenic...


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Combined innate and adaptive immunotherapy overcomes resistance of immunologically cold syngeneic murine neuroblastoma to checkpoint inhibition

Unlike some adult cancers, most pediatric cancers are considered immunologically cold and generally less responsive to immunotherapy. While immunotherapy has already been incorporated into standard of care treatment for pediatric patients with high-risk neuroblastoma, overall survival remains...


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Functional characterization of the selective pan-allele anti-SIRPα antibody ADU-1805 that blocks the SIRPα–CD47 innate immune checkpoint

Accumulating preclinical data indicate that targeting the SIRPα/CD47 axis alone or in combination with existing targeted therapies or immune checkpoint inhibitors enhances tumor rejection. Although several CD47-targeting agents are currently in phase I clinical trials and demonstrate activity in...