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Overcoming resistance to anti-PD1 and anti-PD-L1 treatment in gastrointestinal malignancies

In the last few years, the unprecedented results of immune checkpoint inhibitors have led to a paradigm shift in clinical practice for the treatment of several cancer types. However, the vast majority of patients with gastrointestinal cancer do not benefit from immunotherapy. To date,...


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EpCAM-high liver cancer stem cells resist natural killer cell–mediated cytotoxicity by upregulating CEACAM1

Natural killer (NK) cells can recognize and kill cancer cells directly, but their activity can be attenuated by various inhibitory molecules expressed on the surface. The expression of epithelial cell adhesion molecule (EpCAM), a potential marker for cancer stem cells (CSCs), is known to be...


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Randomized phase II study of the Bruton tyrosine kinase inhibitor acalabrutinib, alone or with pembrolizumab in patients with advanced pancreatic cancer

The immunosuppressive desmoplastic stroma of pancreatic cancer represents a major hurdle to developing an effective immune response. Preclinical studies in pancreatic cancer have demonstrated promising anti-tumor activity with Bruton tyrosine kinase (BTK) inhibition combined with programmed cell...


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Chemotherapy accelerates immune-senescence and functional impairments of Vδ2pos T cells in elderly patients affected by liver metastatic colorectal cancer

Human (gamma delta) γδ T cells are unconventional innate-like lymphocytes displaying a broad array of anti-tumor activities with promising perspectives in cancer immunotherapy. In this context, Vδ2 pos T cells represent the preferential target of several immunotherapy protocols against solid...




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Immunopeptidomics of colorectal cancer organoids reveals a sparse HLA class I neoantigen landscape and no increase in neoantigens with interferon or MEK-inhibitor treatment

Patient derived organoids (PDOs) can be established from colorectal cancers (CRCs) as in vitro models to interrogate cancer biology and its clinical relevance. The authors applied mass spectrometry (MS) immunopeptidomics to investigate neoantigen presentation and whether this can be augmented...


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Treatment with checkpoint inhibitors in a metastatic colorectal cancer patient with molecular and immunohistochemical heterogeneity in MSI/dMMR status

Analysis of deficiency in DNA mismatch repair (dMMR) is currently considered a standard molecular test in all patients with colorectal cancer (CRC) for its implications in screening, prognosis and prediction of benefit from immune checkpoint inhibitors. While the molecular heterogeneity of CRC...


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Comprehensive immune profiling and immune-monitoring using body fluid of patients with metastatic gastric cancer

The aim of this study is to profile the cytokines and immune cells of body fluid from metastatic gastric cancer (mGC), and evaluate the potential role as a prognostic factor and the feasibility as a predictive biomarker or monitoring source for immune checkpoint inhibitor. The authors conclude...


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Immunotherapy in hepatocellular carcinoma: the complex interface between inflammation, fibrosis, and the immune response

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and confers a poor prognosis. Beyond standard systemic therapy with multikinase inhibitors, recent studies demonstrate the potential for robust and durable responses from immune checkpoint inhibition in subsets...