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      The B-Side of Cancer Immunity: The Underrated Tune

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          Abstract

          Tumor-infiltrating lymphocytes are known to be critical in controlling tumor progression. While the role of T lymphocytes has been extensively studied, the function of B cells in this context is still ill-defined. In this review, we propose to explore the role of B cells in tumor immunity. First of all we define their dual role in promoting and inhibiting cancer progression depending on their phenotype. To continue, we describe the influence of different tumor microenvironment factors such as hypoxia on B cells functions and differentiation. Finally, the role of B cells in response to therapy and as potential target is examined. In accordance with the importance of B cells in immuno-oncology, we conclude that more studies are required to throw light on the precise role of B cells in the tumor microenvironment in order to have a better understanding of their functions, and to design new strategies that efficiently target these cells by immunotherapy.

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          Most cited references75

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          Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses

          To guide the design of immunotherapy strategies for patients with early stage lung tumors, we developed a multiscale immune profiling strategy to map the immune landscape of early lung adenocarcinoma lesions to search for tumor-driven immune changes. Utilizing a barcoding method that allows a simultaneous single cell analysis of the tumor, non-involved lung and blood cells together with multiplex tissue imaging to assess spatial cell distribution, we provide a detailed immune cell atlas of early lung tumors. We show that stage I lung adenocarcinoma lesions already harbor significantly altered T cell and NK cell compartments. Moreover, we identified changes in tumor infiltrating myeloid cell (TIM) subsets that likely compromise anti-tumor T cell immunity. Paired single cell analyses thus offer valuable knowledge of tumor-driven immune changes, providing a powerful tool for the rational design of immune therapies. Comparing single tumor cells with adjacent normal tissue and blood from patients with lung adenocarcinoma charts early changes in tumor immunity and provides insights to guide immunotherapy design.
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            Regulatory T cells, tumour immunity and immunotherapy.

            Tumours express a range of antigens, including self-antigens. Regulatory T cells are crucial for maintaining T-cell tolerance to self-antigens. Regulatory T cells are thought to dampen T-cell immunity to tumour-associated antigens and to be the main obstacle tempering successful immunotherapy and active vaccination. In this Review, I consider the nature and characteristics of regulatory T cells in the tumour microenvironment and their potential multiple suppressive mechanisms. Strategies for therapeutic targeting of regulatory T cells and the effect of regulatory T cells on current immunotherapeutic and vaccine regimens are discussed.
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              Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer

              Single-cell transcriptome profiling of tumour tissue isolates allows the characterization of heterogeneous tumour cells along with neighbouring stromal and immune cells. Here we adopt this powerful approach to breast cancer and analyse 515 cells from 11 patients. Inferred copy number variations from the single-cell RNA-seq data separate carcinoma cells from non-cancer cells. At a single-cell resolution, carcinoma cells display common signatures within the tumour as well as intratumoral heterogeneity regarding breast cancer subtype and crucial cancer-related pathways. Most of the non-cancer cells are immune cells, with three distinct clusters of T lymphocytes, B lymphocytes and macrophages. T lymphocytes and macrophages both display immunosuppressive characteristics: T cells with a regulatory or an exhausted phenotype and macrophages with an M2 phenotype. These results illustrate that the breast cancer transcriptome has a wide range of intratumoral heterogeneity, which is shaped by the tumour cells and immune cells in the surrounding microenvironment.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                13 May 2019
                May 2019
                : 8
                : 5
                : 449
                Affiliations
                Tumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, L-1526 Luxenbourg, Luxembourg; anne.largeot@ 123456lih.lu (A.L.); giulia.pagano@ 123456lih.lu (G.P.); susanne.gonder@ 123456lih.lu (S.G.)
                Author notes
                [* ]Correspondence: etienne.moussay@ 123456lih.lu (E.M); jerome.paggetti@ 123456lih.lu (J.P.); Tel.: +35226970-232 (E.M.); +35226970-344 (J.P.)
                [†]

                These authors contributed equally.

                [‡]

                These authors share senior authorship.

                Author information
                https://orcid.org/0000-0002-9388-8461
                https://orcid.org/0000-0001-9460-5876
                Article
                cells-08-00449
                10.3390/cells8050449
                6562515
                31086070
                ca6cfdd7-2ec7-48c6-8daf-a68a0fa5cb6c
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 April 2019
                : 10 May 2019
                Categories
                Review

                b lymphocytes,tumor microenvironment,immunotherapy,tumor immunity,breg

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