B cells, plasma cells and antibody repertoires in the tumour microenvironment

Nature reviews. Immunology, Год журнала: 2020, Номер 20(5), С. 294 - 307

Опубликована: Янв. 27, 2020

Язык: Английский

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TGF-β-associated extracellular matrix genes link cancer-associated fibroblasts to immune evasion and immunotherapy failure

Nature Communications, Год журнала: 2018, Номер 9(1)

Опубликована: Ноя. 2, 2018

The extracellular matrix (ECM) is a key determinant of cancer progression and prognosis. Here we report findings from one the largest pan-cancer analyses ECM gene dysregulation in cancer. We define distinct set genes upregulated (C-ECM) linked to worse found that C-ECM transcriptional programme correlated with activation TGF-β signalling cancer-associated fibroblasts immunosuppression otherwise immunologically active tumours. Cancers activate this carry genomic profiles, such as BRAF, SMAD4 TP53 mutations MYC amplification. Finally, show signature predictor failure PD-1 blockade outperforms previously-proposed biomarkers. Thus, our identify pattern operation across cancers may be potentially targeted, pending preclinical validation, using enhance responses immune-checkpoint blockade.

Язык: Английский

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Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids

Cancer Discovery, Год журнала: 2017, Номер 8(2), С. 196 - 215

Опубликована: Ноя. 4, 2017

Ex vivo systems that incorporate features of the tumor microenvironment and model dynamic response to immune checkpoint blockade (ICB) may facilitate efforts in precision immuno-oncology development effective combination therapies. Here, we demonstrate ability interrogate ex ICB using murine- patient-derived organotypic spheroids (MDOTS/PDOTS). MDOTS/PDOTS isolated from mouse human tumors retain autologous lymphoid myeloid cell populations respond short-term three-dimensional microfluidic culture. Response resistance was recapitulated MDOTS derived established immunocompetent models. profiling demonstrated TBK1/IKKε inhibition enhanced PD-1 blockade, which effectively predicted Systematic secreted cytokines PDOTS captured key associated with blockade. Thus, represents a novel platform evaluate murine models as well clinically relevant patient specimens.Significance: Resistance remains challenge for many patients, biomarkers guide treatment are lacking. feasibility microenvironment, develop therapeutic combinations, efforts. Cancer Discov; 8(2); 196-215. ©2017 AACR.See related commentary by Balko Sosman, p. 143See article Deng et al., 216This is highlighted In This Issue feature, 127.

Язык: Английский

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CD4 and CD8 T lymphocyte interplay in controlling tumor growth

Cellular and Molecular Life Sciences, Год журнала: 2017, Номер 75(4), С. 689 - 713

Опубликована: Окт. 14, 2017

The outstanding clinical success of immune checkpoint blockade has revived the interest in underlying mechanisms system that are capable eliminating tumors even advanced stages. In this scenario, CD4 and CD8 T cell responses part cancer cycle both populations significantly influence outcome. general, evolved several to protect host against cancer. Each them be undermined or evaded during development enable tumor outgrowth. review, we give an overview lymphocyte-driven control growth discuss involved tumor-suppressive system, such as senescence surveillance, immunosurveillance, immunoediting with respect recent developments immunotherapies. main focus is on currently existing knowledge about lymphocyte interplay mediates growth.

Язык: Английский

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Neoantigens: promising targets for cancer therapy

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Янв. 6, 2023

Abstract Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by cells as a result various tumor-specific alterations, such genomic mutation, dysregulated RNA splicing, disordered post-translational modification, integrated viral open reading frames. recognized non-self trigger an immune response that is not subject to central peripheral tolerance. The quick identification prediction neoantigens been made possible advanced next-generation sequencing bioinformatic technologies. Compared tumor-associated antigens, highly immunogenic provide emerging targets personalized serve prospective predictors survival prognosis checkpoint blockade responses. therapies will be aided understanding mechanism underlying neoantigen-induced anti-tumor streamlining process neoantigen-based immunotherapies. This review provides overview on characterization outlines clinical applications immunotherapeutic strategies based neoantigens. We also explore their current status, inherent challenges, translation potential.

Язык: Английский

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