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      T lymphocyte subsets in cancer immunity: Friends or foes

      1 , 2 , 1 , 3 , 2 , 1
      Journal of Leukocyte Biology
      Wiley

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          Abstract

          Although immune-based therapy is proving to be a success in several cancer types, only a set of patients appear to respond to immune checkpoint blockade including PD-1 and CTLA-4. A better understanding of the crucial components of cancer immunity is therefore necessary. T lymphocytes, a key element, are found within the tumor microenvironment and seem to be critical in determining the efficacy of immune surveillance. In this review, we will depict the pro- and antitumor roles of major T cell subsets in distinct cancer tissues. The central role of the mainly antitumor subsets, cytotoxic T cells and Th1 cells, will be delineated. Subsequently, we will indicate how other subsets including Th2, Th17, and T regulatory cells exhibit ambivalent roles. We will also describe the emerging and favorable role of Th9 cells in cancer immunity. In parallel, we will go through main mechanisms by which these cells operate, and will pinpoint pathways, which could be used as potential therapeutic targets in order to positively impact the immune response and ameliorate patients' clinical outcome.

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          Most cited references105

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          Stromal gene expression predicts clinical outcome in breast cancer.

          Although it is increasingly evident that cancer is influenced by signals emanating from tumor stroma, little is known regarding how changes in stromal gene expression affect epithelial tumor progression. We used laser capture microdissection to compare gene expression profiles of tumor stroma from 53 primary breast tumors and derived signatures strongly associated with clinical outcome. We present a new stroma-derived prognostic predictor (SDPP) that stratifies disease outcome independently of standard clinical prognostic factors and published expression-based predictors. The SDPP predicts outcome in several published whole tumor-derived expression data sets, identifies poor-outcome individuals from multiple clinical subtypes, including lymph node-negative tumors, and shows increased accuracy with respect to previously published predictors, especially for HER2-positive tumors. Prognostic power increases substantially when the predictor is combined with existing outcome predictors. Genes represented in the SDPP reveal the strong prognostic capacity of differential immune responses as well as angiogenic and hypoxic responses, highlighting the importance of stromal biology in tumor progression.
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            The Where, the When, and the How of Immune Monitoring for Cancer Immunotherapies in the Era of Checkpoint Inhibition.

            Clinical trials with immune checkpoint inhibitors have provided important insights into the mode of action of anticancer immune therapies and potential mechanisms of immune escape. Development of the next wave of rational clinical combination strategies will require a deep understanding of the mechanisms by which combination partners influence the battle between the immune system's capabilities to fight cancer and the immune-suppressive processes that promote tumor growth. This review focuses on our current understanding of tumor and circulating pharmacodynamic correlates of immune modulation and elaborates on lessons learned from human translational research with checkpoint inhibitors. Actionable tumor markers of immune activation including CD8(+)T cells, PD-L1 IHC as a pharmacodynamic marker of T-cell function, T-cell clonality, and challenges with conduct of trials that ask scientific questions from serial biopsies are addressed. Proposals for clinical trial design, as well as future applications of peripheral pharmacodynamic endpoints as potential surrogates of early clinical activity, are discussed. On the basis of emerging mechanisms of response and immune escape, we propose the concept of the tumor immunity continuum as a framework for developing rational combination strategies.
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              Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer.

              The tumor microenvironment includes a complex network of immune T-cell subpopulations. In this study, we systematically analyzed the balance between cytotoxic T cells and different subsets of helper T cells in human colorectal cancers and we correlated their impact on disease-free survival. A panel of immune related genes were analyzed in 125 frozen colorectal tumor specimens. Infiltrating cytotoxic T cells, Treg, Th1, and Th17 cells were also quantified in the center and the invasive margin of the tumors. By hierarchical clustering of a correlation matrix we identified functional clusters of genes associated with Th17 (RORC, IL17A), Th2 (IL4, IL5, IL13), Th1 (Tbet, IRF1, IL12Rb2, STAT4), and cytotoxicity (GNLY, GZMB, PRF1). Patients with high expression of the Th17 cluster had a poor prognosis, whereas patients with high expression of the Th1 cluster had prolonged disease-free survival. In contrast, none of the Th2 clusters were predictive of prognosis. Combined analysis of cytotoxic/Th1 and Th17 clusters improved the ability to discriminate relapse. In situ analysis of the density of IL17+ cells and CD8+ cells in tumor tissues confirmed the results. Our findings argue that functional Th1 and Th17 clusters yield opposite effects on patient survival in colorectal cancer, and they provide complementary information that may improve prognosis. ©2011 AACR.
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                Author and article information

                Journal
                Journal of Leukocyte Biology
                J Leukoc Biol
                Wiley
                0741-5400
                1938-3673
                December 21 2018
                February 2019
                November 02 2018
                February 2019
                : 105
                : 2
                : 243-255
                Affiliations
                [1 ]Cellular and Molecular Pathology LaboratoryFaculty of Medicine and Pharmacy of CasablancaHassan II University Casablanca Morocco
                [2 ]Team Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS, UMR7258Institut Paoli‐CalmettesAix‐Marseille University, UM 105 Marseille France
                [3 ]University Mohammed VI for Health ScienceCheick Khalifa Hospital Casablanca Morocco
                Article
                10.1002/JLB.MR0318-097R
                30387907
                77d6d1ce-58a4-4420-b5ac-2d25c8f8231a
                © 2019

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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