4 results
Search Results
2. Metabolic manipulation of the tumour immune microenvironment.
- Author
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Wan, Mengtian, Ding, Yuzhu, Li, Zheng, Wang, Xu, and Xu, Min
- Subjects
TUMOR microenvironment ,CANCER cells ,CANCER treatment - Abstract
In the past few years, the evolution of immunotherapy has resulted in a shift in cancer treatment models. However, with immunosuppressive effects of the tumour microenvironment continues to limit advances in tumour immunotherapy. The tumour microenvironment induces metabolic reprogramming in cancer cells, which results in competition for nutrients between tumour cells and host immunocytes. Metabolic and waste products originating in tumour cells can influence the activation and effector properties of immunocytes in numerous ways and ultimately promote the survival and propagation of tumour cells. In this paper, we discuss metabolic reprogramming in tumour cells and the influence of metabolite by‐products on the immune microenvironment, providing novel insights into tumour immunotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
3. Identification of neoantigens in oesophageal adenocarcinoma.
- Author
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Nicholas, Ben, Bailey, Alistair, McCann, Katy J., Wood, Oliver, Walker, Robert C., Parker, Robert, Ternette, Nicola, Elliott, Tim, Underwood, Tim J., Johnson, Peter, and Skipp, Paul
- Subjects
ADENOCARCINOMA ,PEPTIDES ,LEUCOCYTES ,IMMUNOTHERAPY ,T cells - Abstract
Oesophageal adenocarcinoma (OAC) has a relatively poor long‐term survival and limited treatment options. Promising targets for immunotherapy are short peptide neoantigens containing tumour mutations, presented to cytotoxic T‐cells by human leucocyte antigen (HLA) molecules. Despite an association between putative neoantigen abundance and therapeutic response across cancers, immunogenic neoantigens are challenging to identify. Here we characterized the mutational and immunopeptidomic landscapes of tumours from a cohort of seven patients with OAC. We directly identified one HLA‐I presented neoantigen from one patient, and report functional T‐cell responses from a predicted HLA‐II neoantigen in a second patient. The predicted class II neoantigen contains both HLA I and II binding motifs. Our exploratory observations are consistent with previous neoantigen studies in finding that neoantigens are rarely directly observed, and an identification success rate following prediction in the order of 10%. However, our identified putative neoantigen is capable of eliciting strong T‐cell responses, emphasizing the need for improved strategies for neoantigen identification. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
4. Oncolytic virus treatment differentially affects the CD56dim and CD56bright NK cell subsets in vivo and regulates a spectrum of human NK cell activity.
- Author
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Wantoch, Michelle, Wilson, Erica B., Droop, Alastair P., Phillips, Sarah L., Coffey, Matt, El‐Sherbiny, Yasser M., Holmes, Tim D., Melcher, Alan A., Wetherill, Laura F., and Cook, Graham P.
- Subjects
KILLER cells ,TYPE I interferons ,LYMPHOID tissue ,PERIPHERAL circulation ,GENE expression profiling - Abstract
Natural killer (NK) cells protect against intracellular infection and cancer. These properties are exploited in oncolytic virus (OV) therapy, where antiviral responses enhance anti‐tumour immunity. We have analysed the mechanism by which reovirus, an oncolytic dsRNA virus, modulates human NK cell activity. Reovirus activates NK cells in a type I interferon (IFN‐I) dependent manner, inducing STAT1 and STAT4 signalling in both CD56dim and CD56bright NK cell subsets. Gene expression profiling revealed the dominance of IFN‐I responses and identified induction of genes associated with NK cell cytotoxicity and cell cycle progression, with distinct responses in the CD56dim and CD56bright subsets. However, reovirus treatment inhibited IL‐15 induced NK cell proliferation in an IFN‐I dependent manner and was associated with reduced AKT signalling. In vivo, human CD56dim and CD56bright NK cells responded with similar kinetics to reovirus treatment, but CD56bright NK cells were transiently lost from the peripheral circulation at the peak of the IFN‐I response, suggestive of their redistribution to secondary lymphoid tissue. Coupled with the direct, OV‐mediated killing of tumour cells, the activation of both CD56dim and CD56bright NK cells by antiviral pathways induces a spectrum of activity that includes the NK cell‐mediated killing of tumour cells and modulation of adaptive responses via the trafficking of IFN‐γ expressing CD56bright NK cells to lymph nodes. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
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