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Simultaneous inhibition of CXCR1/2, TGF-β, and PD-L1 remodels the tumor and its microenvironment to drive antitumor immunity

Despite the success of immune checkpoint blockade therapy in the treatment of certain cancer types, only a small percentage of patients with solid malignancies achieve a durable response. Consequently, there is a need to develop novel approaches that could overcome mechanisms of tumor resistance...


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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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A case of dual-mechanism immune-related anaemia in a patient with metastatic melanoma treated with nivolumab and ipilimumab

The combination of the immune checkpoint inhibitors (ICIs) ipilimumab and nivolumab is a mainstay of treatment for selected patients with metastatic melanoma. This combination also results in more frequent immune-related adverse events (irAEs) than either ICI alone. These irAEs can be severe and...


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Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab

This case represents an exceptional response to pembrolizumab in a patient with epithelioid mesothelioma with a further response on rechallenge. A 77-year-old woman with advanced epithelioid mesothelioma extensively pretreated with chemotherapy demonstrated a prolonged response of 45 months to...


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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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TriMix and tumor antigen mRNA electroporated dendritic cell vaccination plus ipilimumab: link between T-cell activation and clinical responses in advanced melanoma

The authors previously reported that dendritic cell-based mRNA vaccination plus ipilimumab (TriMixDC-MEL IPI) results in an encouraging rate of tumor responses in patients with pretreated advanced melanoma. Here, they report the TriMixDC-MEL IPI-induced T-cell responses detected in the...


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Comparison of iRECIST versus RECIST V.1.1 in patients treated with an anti-PD-1 or PD-L1 antibody: pooled FDA analysis

Response criteria developed when cytotoxic chemotherapy was the predominant therapeutic modality to treat patients with cancer, do not capture the full spectrum of tumor response patterns observed with anti-PD-1/PD-L1 antibody treatment. iRECIST was developed to capture both typical and atypical...


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Repurposing infectious disease vaccines for intratumoral immunotherapy

Intratumoral delivery of viruses and virus-associated molecular patterns can achieve antitumor effects that are largely mediated by the elicitation or potentiation of immune responses against the malignancy. Attenuated vaccines are approved and marketed as good manufacturing practice (GMP)...


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On the mechanism of anti-CD39 immune checkpoint therapy

With the coming of age of cancer immunotherapy, the search for new therapeutic targets has led to the identification of immunosuppressive adenosine as an important regulator of antitumor immunity. This resulted in the development of selective inhibitors targeting various components of the...


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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...