Reconstructed Adeno-Associated Virus with the Extracellular Domain of Murine PD-1 Induces Antitumor Immunity

Elhag, Osama A.O.; Hu, Xiaojing; Zhang, Wenying; Li, Xiong; Yuan, Yongze; Deng, Lei; Liu, De Li; Liu, Yingle; Geng, Hui

doi:10.7314/apjcp.2012.13.8.4031

Cited by 49 publications

(50 citation statements)

References 36 publications

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“…Regarding sPD-1, an elevated sPD-1 level was associated with prolonged OS ( P = 0.006) and progression-free survival ( P = 0.013) for patients with non-small cell lung cancer undergoing erlotinib therapy [12]. In fact, in a previous study of murine HCC, delivery of sPD-1 into tumor site using adeno-associated virus resulted in enhancement of antitumor immune effects and ultimately reduced tumor growth and prolonged long-term survival [22]. Preclinical studies indicated that sPD-1 is bioactive, which could counteract the immunosuppressive effect of the PD-1/PD-L1 pathway, leading to restored T-cell function, a decreased number of regulatory T cells and enhanced antitumor immunity [23, 24].…”

Section: Discussionmentioning

confidence: 99%

The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma

Chang

Huang

Wei

et al. 2018

Cancer Immunol Immunother

105

104

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BackgroundBlocking the programmed death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in hepatocellular carcinoma (HCC) is a very promising approach in immunotherapy. However, the correlation and prognostic values of serum soluble PD-1 and PD-L1 (sPD-1/sPD-L1) have not been explored conjointly in HCC patients.MethodsThis study retrospectively included 120 HCC patients receiving radical resection. The serum levels of sPD-1/sPD-L1 and inflammatory cytokines were measured by antibody array assay. Immunohistochemistry was applied to assess both the expression of membrane-bound PD-L1, and the number of CD4+ tumor-infiltrating lymphocytes (TILs) and CD8+ TILs.ResultsThe best cut-off values of sPD-1 and sPD-L1 for predicting disease-free survival (DFS) were 33.0 µg/ml and 11.2 µg/ml, respectively. Multivariable analysis showed that sPD-L1 was a negative independent prognostic factor [DFS, Hazard Ratio (HR) 2.58, 95% CI 1.14–5.84, P = 0.023; overall survival (OS), HR 1.77, 95% CI 1.01–3.12, P = 0.048], while sPD-1 was a favorable independent prognostic factor (DFS, HR 0.32, 95% CI 0.14–0.74, P = 0.007; OS, HR 0.54, 95% CI 0.30–0.98, P = 0.044) in HCC patients. We also observed some similar associations between inflammatory cytokines (IL-10, IL-17, TNF-α) and sPD-1 or sPD-L1, as well as a close positive association between sPD-1 and sPD-L1. No significant associations of sPD-1/sPD-L1 with either intra-tumoral PD-L1 expression, or the numbers of CD4+ TILs and CD8+ TILs were determined.ConclusionsOur findings indicate that sPD-1 and sPD-L1 are independent prognostic factors with opposite prognostic roles in predicting both DFS and OS in HCC patients.Electronic supplementary materialThe online version of this article (10.1007/s00262-018-2271-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma

Chang

Huang

Wei

et al. 2018

Cancer Immunol Immunother

105

104

View full text Add to dashboard Cite

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“…B7-H1 mRNA is widespread in human tissues, although cell surface protein expression is restricted to a fraction of macrophagelineage cells (Dong et al, 1999;Dong et al, 2002). B7-H1 can be found on activated T lymphocytes and aberrantly expressed by numerous human tumors (Dong et al, 2002;Wintterle et al, 2003;Curiel et al, 2003;Jun Konishi et al, 2004;Ohigashi et al, 2005., Elhag et al, 2012. Experimental evidences suggested that human ovary tumor and its tumor-infiltrating macrophages also highly expressed B7-H1 (Dong et al, 2002;Dong et al, 2003), but the underlying mechanism for the upregulation remains unclear.…”

Section: Il-12 Regulates B7-h1 Expression In Ovarian Cancerassociatedmentioning

confidence: 99%

IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling

Xiong¹,

Ma²,

Wu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…TLR4 antagonists have been developed for the treatment of several cancers and antibodies blockade of B7-H1 have been shown to potentiate antitumoral immunity in vitro and in vivo (Sun et al, 2008;Okudaira et al, 2009;Hasan et al, 2011;Elhag et al, 2012). Moreover, it is well known that TLR4 may involve in the response to BCG during BCG immunotherapy for bladder cancer.…”

Section: 1321 Effect Of Tlr4 and B7-h1 On The Immune Escape Of Urothmentioning

confidence: 99%

Effect of TLR4 and B7-H1 on Immune Escape of Urothelial Bladder Cancer and its Clinical Significance

Wang

Cao²,

Yang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background/Aim: Toll-like receptor 4 (TLR4) and B7-H1, both normally expressed restricted to immune cells, are found to be aberrantly expressed in a majority of human tumors and may play important roles in regulation of tumor immunity. It has been shown that urothelial bladder cancer (UBC) patients can manifest tumoral immune escape which may be a potential critical factor in tumor pathogenesis and progression. However, so far, the mechanisms of UBC-related immune escape have not been clarified. The aim of this study was to investigate the effect of TLR4 and B7-H1 on immune escape of UBC. Methods: Bladder cancer T24 cells were pre-incubated with LPS and co-cultured with tumor specific CTLs. CTL cytotoxicity and apoptosis rates were measured by MTT assay and flow cytometry, respectively. The effects of an ERK inhibitor on B7-H1 expression and CTL cytotoxicity against T24 cells were also evaluated. In addition, TLR4, B7-H1 and PD-1 protein expression was analyzed by immunohistochemistry in 60 UBC specimens and 10 normal urothelia. Results: TLR4 activation protected T24 cells from CTL killing via B7-H1 overexpression. However PD98059, an inhibitor of ERK, enhanced CTL killing of T24 cells by reducing B7-H1 expression. TLR4 expression was generally decreased in UBC specimens, while B7-H1 and PD-1 were greatly overexpressed. Moreover, expression of both B7-H1 and PD-1 was significantly associated with UICC stage and WHO grade classification. Conclusions: TLR4 and B7-H1 may contribute to immune escape of UBC. Targeting B7-H1 or the ERK pathway may offer new immunotherapy strategies for bladder cancer.

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Reconstructed Adeno-Associated Virus with the Extracellular Domain of Murine PD-1 Induces Antitumor Immunity

Cited by 49 publications

References 36 publications

The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma

The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma

IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling

Effect of TLR4 and B7-H1 on Immune Escape of Urothelial Bladder Cancer and its Clinical Significance

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