Soluble B7-H1: Differences in production between dendritic cells and T cells

Frigola, Xavier; Inman, Brant A.; Krco, Christopher J.; Liu, Xin; Harrington, Susan M.; Bulur, Peggy A.; Dietz, Allan B.; Dong, Haidong; Kwon, Eugene D.

doi:10.1016/j.imlet.2011.11.001

Cited by 120 publications

(126 citation statements)

References 18 publications

(20 reference statements)

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“…However, the underlying pathogenesis remains unclear. Amarnath et al ( Although both myeloid and T lymphocytes exhibit mPD-L1 expression, the release of sPD-L1 is a feature of the myeloid population (32,33). The results of the present study demonstrated that the expression levels of sPD-L1 in PF were increased, as compared with PB; this may be due to the high concentrations of cytokines in the local pleural cavity.…”

Section: A B Csupporting

confidence: 49%

Increased soluble and membrane-bound PD-L1 contributes to immune regulation and disease progression in patients with tuberculous pleural effusion

Pan

Zhong

Xing

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Soluble and membrane-bound programmed death ligand-1 (sPD-L1 and mPD-L1, respectively) have been demonstrated to participate in the immune suppression of non-small cell lung cancer. However, the contribution of sPD-L1 and mPD-L1 to immune regulation and disease progression in patients with pleural effusions remains unknown. The present study evaluated the levels of sPD-L1 and membrane-bound PD-1/PD-L1 in the peripheral blood and pleural effusions of patients with tuberculous pleural effusion (TPE), malignant pleural effusion (MPE) and non-tuberculous non-malignant pleural effusion (n-TB n-M). Furthermore, selected T lymphocytes and cluster of differentiation (CD)14 + monocytes were co-cultured to investigate the potential effect of the PD-1/PD-L1 pathway in TPE. Levels of sPD-L1 and PD-L1 on CD14 + monocytes were increased in the TPE group, as compared with the MPE and n-TB n-M groups. Furthermore, sPD-L1 levels and the expression levels of PD-L1 on CD14 + monocytes were demonstrated to be positively correlated with interferon (IFN)-γ concentration in pleural effusions. Therefore, IFN-γ may increase the expression of PD-L1 on CD14 + monocytes in vitro. Cell counting kit-8 analysis demonstrated that anti-PD-L1 antibody was able to partially reverse the proliferation of T lymphocytes in the co-culture system. The results of the present study indicated that sPD-L1 or mPD-L1 are associated with the immune regulation and disease progression of TPE, and may serve as possible biomarkers of TPE. Furthermore, sPD-L1 and the PD-1/PD-L1 pathway of TPE may be associated with the Th1 immune response; therefore, an anti-PD-1/PD-L1 pathway suggests a potential immune therapy strategy for the treatment of TPE.

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Section: A B Csupporting

confidence: 49%

Increased soluble and membrane-bound PD-L1 contributes to immune regulation and disease progression in patients with tuberculous pleural effusion

Pan

Zhong

Xing

et al. 2016

Experimental and Therapeutic Medicine

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“…The results of Fig. 4C shows that DNA-PKcs and B7-H1 in Karpas 299 were mutually pulled down by their respective antibodies20. Significantly, an association of DNA-PKcs and B7-H1 was detected in activated (known to up-regulate B7-H1 expression) but not resting human T cells (Fig.…”

Section: Resultsmentioning

confidence: 85%

B7-H1 antibodies lose antitumor activity due to activation of p38 MAPK that leads to apoptosis of tumor-reactive CD8+ T cells

Liu¹,

Wu²,

Cao³

et al. 2016

Sci Rep

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B7-H1 (aka PD-L1) blocking antibodies have been used in treatment of human cancers through blocking B7-H1 expressed by tumor cells; however, their impact on B7-H1 expressing tumor-reactive CD8+ T cells is still unknown. Here, we report that tumor-reactive CD8+ T cells expressing B7-H1 are functional effector cells. In contrast to normal B7-H1 blocking antibody, B7-H1 antibodies capable of activating p38 MAPK lose their antitumor activity by deleting B7-H1+ tumor-reactive CD8+ T cells via p38 MAPK pathway. B7-H1 deficiency or engagement with certain antibody results in more activation of p38 MAPK that leads to T cell apoptosis. DNA-PKcs is a new intracellular partner of B7-H1 in the cytoplasm of activated CD8+ T cells. B7-H1 suppresses p38 MAPK activation by sequestering DNA-PKcs in order to preserve T cell survival. Our findings provide a new mechanism of action of B7-H1 in T cells and have clinical implications in cancer immunotherapy when anti-B7-H1 (PD-L1) antibody is applied.

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“…24,25 It has also been shown that sPD-L1 is produced and released by activated mature dendritic cells and suggested that immune and tumour cells could be the source of soluble PD-L1. 26 Measuring sPD-L1 may be a surrogate marker for surface PD-L1, which could be readily tested in the clinic with a blood test. Further work is required to explore whether these immunological markers in blood are raised in other conditions of inflammation, chronic infection and autoimmunity to establish their efficacy as diagnostic biomarkers and also to monitor response to therapy or recurrence of disease.…”

Section: Validation Of the Significant Immune Markers By Immunohistocmentioning

confidence: 99%

Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer

Chatterjee

Dai

Aziz

et al. 2017

Clinical Cancer Research

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Purpose: We aimed to establish whether programmed cell death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression, in ovarian cancer tumor tissue and blood, could be used as biomarkers for discrimination of tumor histology and prognosis of ovarian cancer. Experimental Design: Immune cells were separated from blood, ascites, and tumor tissue obtained from women with suspected ovarian cancer and studied for the differential expression of possible immune biomarkers using flow cytometry. PD-L1 expression on tumor-associated inflammatory cells was assessed by immunohistochemistry and tissue microarray. Plasma soluble PD-L1 was measured using sandwich ELISA. The relationships among immune markers were explored using hierarchical cluster analyses. Results: Biomarkers from the discovery cohort that associated with PD-L1+ cells were found. PD-L1+ CD14+ cells and PD-L1+ CD11c+ cells in the monocyte gate showed a distinct expression pattern when comparing benign tumors and epithelial ovarian cancers (EOCs)—confirmed in the validation cohort. Receiver operating characteristic curves showed PD-L1+ and PD-L1+ CD14+ cells in the monocyte gate performed better than the well-established tumor marker CA-125 alone. Plasma soluble PD-L1 was elevated in patients with EOC compared with healthy women and patients with benign ovarian tumors. Low total PD-1+ expression on lymphocytes was associated with improved survival. Conclusions: Differential expression of immunological markers relating to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers in EOC. These data have implications for the development and trial of anti–PD-1/PD-L1 therapy in ovarian cancer. Clin Cancer Res; 23(13); 3453–60. ©2016 AACR.

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Soluble B7-H1: Differences in production between dendritic cells and T cells

Cited by 120 publications

References 18 publications

Increased soluble and membrane-bound PD-L1 contributes to immune regulation and disease progression in patients with tuberculous pleural effusion

Increased soluble and membrane-bound PD-L1 contributes to immune regulation and disease progression in patients with tuberculous pleural effusion

B7-H1 antibodies lose antitumor activity due to activation of p38 MAPK that leads to apoptosis of tumor-reactive CD8+ T cells

Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer

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