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ARID1A alterations function as a biomarker for longer progression-free survival after anti-PD-1/PD-L1 immunotherapy

Several cancer types harbor alterations in the gene encoding AT-Rich Interactive Domain-containing protein 1A (ARID1A), but there are no approved therapies to address these alterations. Recent studies have shown that ARID1A deficiency compromises mismatch repair proteins. The authors...


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Identification of tumor immune infiltration-associated lncRNAs for improving prognosis and immunotherapy response of patients with non-small cell lung cancer

Increasing evidence has demonstrated the functional relevance of long non-coding RNAs (lncRNAs) to immunity regulation and the tumor microenvironment in non-small cell lung cancer (NSCLC). However, tumor immune infiltration-associated lncRNAs and their value in improving clinical outcomes and...


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Increased antitumor efficacy of PD-1-deficient melanoma-specific human lymphocytes

Genome editing offers unique perspectives for optimizing the functional properties of T cells for adoptive cell transfer purposes. So far, PDCD1 editing has been successfully tested mainly in chimeric antigen receptor T (CAR-T) cells and human primary T cells. Nonetheless, for patients with...


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Genetic instability as a driver for immune surveillance

Genetic instability is known to relate with carcinogenesis by providing tumors with a mechanism for fast adaptation. However, mounting evidence also indicates causal relation between genetic instability and improved cancer prognosis resulting from efficient immune response. Highly unstable...


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IL-17 inhibits CXCL9/10-mediated recruitment of CD8+ cytotoxic T cells and regulatory T cells to colorectal tumors

The IL-17 family cytokines are potent drivers of colorectal cancer (CRC) development. The authors and others have shown that IL-17 mainly signals to tumor cells to promote CRC, but the underlying mechanism remains unclear. IL-17 also dampens Th1-armed anti-tumor immunity, in part by attracting...


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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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Mechanisms regulating PD-L1 expression on tumor and immune cells

The PD-1/PD-L1 checkpoint is a central mediator of immunosuppression in the tumor immune microenvironment (TME) and is primarily associated with IFN-g signaling. To characterize other factors regulating PD-L1 expression on tumor and/or immune cells, the authors investigated TME-resident...


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CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma

Despite remarkable success in the treatment of hematological malignancies, CAR T-cell therapies for solid tumors have floundered, in large part due to local immune suppression and the effects of prolonged stimulation leading to T-cell dysfunction and exhaustion. One mechanism by which gliomas...


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Secondary resistance to immunotherapy associated with β-catenin pathway activation or PTEN loss in metastatic melanoma

While cancer immunotherapies including checkpoint blockade antibodies, adoptive T cell therapy, and even some vaccines have given rise to major clinical responses with durability in many cases, a subset of patients who initially respond subsequently develop secondary resistance to therapy. Tumor...


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Intratumoral immunoglobulin isotypes predict survival in lung adenocarcinoma subtypes

The role of tumor-infiltrating B-cells (TIBs) and intratumorally-produced antibodies in cancer-immunity interactions essentially remains terra incognita . In particular, it remains unexplored how driver mutations could be associated with distinct TIBs signatures and their role in tumor...