Dataset Information

CD72/CD100 and PD-1/PD-L1 markers are increased on T and B cells in HIV-1+ viremic individuals, and CD72/CD100 axis is correlated with T-cell exhaustion.

ABSTRACT: In our work, we analyzed the role of the CD100/CD72 and PD-1/PD-L1 axes in immune response dysfunction in human immunodeficiency virus (HIV)-1 infection in which high expressions of PD-1 and PD-L1 were associated with an immunosuppressive state via limitation of the HIV-1-specific T-cell responses. CD100 was demonstrated to play a relevant role in immune responses in various pathological processes and may be responsible for immune dysregulation during HIV-1 infection. We investigated the function of CD72/CD100, and PD-1/PDL-1 axes on T and B cells in HIV-infected individuals and in healthy individuals. We analyzed the frequencies and fluorescence intensities of these four markers on CD4+, CD8+ T and B cells. Marker expressions were increased during active HIV-1 infection. CD100 frequency on T cells was positively associated with the expression of PD-1 and PD-L1 on T cells from HIV-infected treatment-naïve individuals. In addition, the frequency of CD72-expressing T cells was associated with interferon gamma (IFN-?) production in HIV-infected treatment-naïve individuals. Our data suggest that the CD72/CD100 and PD-1/PD-L1 axes may jointly participate in dysregulation of immunity during HIV-1 infection and could partially explain the immune systems' hyper-activation and exhaustion.

SUBMITTER: Correa-Rocha R

PROVIDER: S-EPMC6117071 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

CD72/CD100 and PD-1/PD-L1 markers are increased on T and B cells in HIV-1+ viremic individuals, and CD72/CD100 axis is correlated with T-cell exhaustion.

Correa-Rocha Rafael R Lopez-Abente Jacobo J Gutierrez Carolina C Pérez-Fernández Verónica Astrid VA Prieto-Sánchez Adrián A Moreno-Guillen Santiago S Muñoz-Fernández María-Ángeles MÁ Pion Marjorie M

PloS one 20180830 8

In our work, we analyzed the role of the CD100/CD72 and PD-1/PD-L1 axes in immune response dysfunction in human immunodeficiency virus (HIV)-1 infection in which high expressions of PD-1 and PD-L1 were associated with an immunosuppressive state via limitation of the HIV-1-specific T-cell responses. CD100 was demonstrated to play a relevant role in immune responses in various pathological processes and may be responsible for immune dysregulation during HIV-1 infection. We investigated the functio ...[more]

PMID: 30161254

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Project description:The induction of exhaustion on effector immune cells is an important limiting factor for cancer immunotherapy efficacy as these cells undergo a hierarchical loss of proliferation and cytolytic activity due to chronic stimulation. Targeting PD-1 has shown unprecedented clinical benefits for many cancers, which have been attributed to the prevention of immune suppression and exhaustion with enhanced anti-tumor responses. In this study, we sought to evaluate the role of the PD-1/PD-L1 pathway in murine natural killer (NK) cell activation, function, and exhaustion. In an in vivo IL-2-dependent exhaustion mouse model, neutralization of the PD-1/PD-L1 pathway improved NK cell activation after chronic stimulation when compared to control-treated mice. These cells displayed higher proliferative capabilities and enhanced granzyme B production. However, the blockade of these molecules during long-term in vitro IL-2 stimulation did not alter the progression of NK cell exhaustion (NCE), suggesting an indirect involvement of PD-1/PD-L1 on NCE. Given the expansion of CD8 T cells and regulatory T cells (Tregs) observed upon acute and chronic stimulation with IL-2, either of these two populations could influence NK cell homeostasis after PD-L1/PD-1 therapy. Importantly, CD8 T cell activation and functional phenotype were indeed enhanced by PD-1/PD-L1 therapy, particularly with anti-PD-1 treatment that resulted in the highest upregulation of CD25 during chronic stimulation and granted an advantage for IL-2 over NK cells. These results indicate a competition for resources between NK and CD8 T cells that arguably delays the onset of NCE rather than improving its activation during chronic stimulation. Supporting this notion, the depletion of CD8 T cells reversed the benefits of PD-1 therapy on chronically stimulated NK cells. These data suggest a bystander effect of anti-PD1 on NK cells, resulting from the global competition that exists between NK and CD8 T cells for IL-2 as a key regulator of these cells' activation. Thus, achieving an equilibrium between these immune cells might be important to accomplish long-term efficacy during anti-PD-1/IL-2 therapy.

Project description:BackgroundProgrammed cell death ligand-1 (PD-L1) and ligand-2 (PD-L2) interaction with programmed cell death protein-1 (PD-1) represent an immune-inhibiting checkpoint mediating immune evasion and is, accordingly, an important target for blockade-based immunotherapy in cancer. In non-small-cell lung cancer (NSCLC), improved understanding of PD-1 checkpoint blockade-responsive biology and identification of biomarkers for prediction of a clinical response to immunotherapy is warranted. Thus, in the present study, we systematically described PD-L1 and PD-L2 expression correlated genes in NSCLC.MethodsWe performed comparative retrospective analyses to identify PD-L1 and PD-L2 mRNA expression correlated genes in NSCLC. For this, we examined available datasets from the cancer cell line encyclopedia (CCLE) project lung non-small-cell (Lung_NSC) and the cancer genome atlas (TCGA) projects lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC).ResultsAnalysis of the CCLE dataset Lung_NSC identified expression correlation between PD-L1 and PD-L2. Moreover, we identified expression correlation between 489 genes and PD-L1, 191 genes and PD-L2, and 111 genes for both. PD-L1 and PD-L2 also expression correlated in TCGA datasets LUAD and LUSC. In LUAD, we identified expression correlation between 257 genes and PD-L1, 914 genes and PD-L2, and 211 genes for both. In LUSC, we identified expression correlation between 26 genes and PD-L1, 326 genes and PD-L2, and 13 genes for both. Only a few genes expression correlated with PD-L1 and PD-L2 across the CCLE and TCGA datasets. Expression of Interferon signaling-involved genes converged in particular with the expression correlated genes for PD-L1 in Lung_NSC, for PD-L2 in LUSC, and for both PD-L1 and PD-L2 in LUAD. In LUSC, PD-L1, and to a lesser extent PD-L2, expression correlated with chromosome 9p24 localized genes, indicating a chromosome 9p24 topologically associated domain as an important driver of in particular LUSC PD-L1 expression. Expression correlation analyses of the PD-L1 and PD-L2 receptors programmed cell death protein-1 (PD-1), Cluster of differentiation 80 (CD80), and Repulsive guidance molecule B (RGMB) showed that PD-1 and CD80 expression correlated with both PD-L1 and PD-L2 in LUAD. CD80 expression correlated with PD-L2 in LUSC.ConclusionsWe present gene signatures associated with PD-L1 and PD-L2 mRNA expression in NSCLC which could possess importance in relation to understand PD-1 checkpoint blockade-responsive biology and development of gene signature based biomarkers for predicting clinical responses to immunotherapy.

Dataset Information

CD72/CD100 and PD-1/PD-L1 markers are increased on T and B cells in HIV-1+ viremic individuals, and CD72/CD100 axis is correlated with T-cell exhaustion.

Publications

CD72/CD100 and PD-1/PD-L1 markers are increased on T and B cells in HIV-1+ viremic individuals, and CD72/CD100 axis is correlated with T-cell exhaustion.

Similar Datasets

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