TLR3-Stimulated Dendritic Cells Up-regulate B7-H1 Expression and Influence the Magnitude of CD8 T Cell Responses to Tumor Vaccination

Pulko, Vesna; Liu, Xin; Krco, Christopher J.; Harris, Kimberly J.; Frigola, Xavier; Kwon, Eugene D.; Dong, Haidong

doi:10.4049/jimmunol.0900974

Cited by 106 publications

(93 citation statements)

References 51 publications

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“…Therefore, a combination of costimulatory stimulation and inhibitory blockage should achieve a synergistic effect on T cell activation, which has been shown in chronic viral infection and tumor therapy (30,31). In the current study, we demonstrate that the combination of TLR1/2 stimulation and PD-L1 blockage has a synergistic effect on LSEC-induced CD8 T cell activation.…”

Section: Discussionsupporting

confidence: 65%

TLR1/2 Ligand–Stimulated Mouse Liver Endothelial Cells Secrete IL-12 and Trigger CD8+ T Cell Immunity In Vitro

Liu

Jiang

et al. 2013

The Journal of Immunology

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Liver sinusoidal endothelial cells (LSECs) are unique organ-resident APCs capable of Ag cross-presentation and subsequent tolerization of naive CD8+ T cells. Under certain conditions, LSECs can switch from a tolerogenic to an immunogenic state and promote the development of T cell immunity. However, little is known about the mechanisms of LSECs to induce T cell immunity. In this study, we investigated whether functional maturation of LSECs can be achieved by TLR ligand stimulation and elucidated the mechanisms involved in LSEC-induced T cell immunity. We demonstrate that pretreatment of LSECs with palmitoyl-3-cysteine-serine-lysine-4 (P3C; TLR1/2 ligand) but not poly(I:C) (TLR3 ligand) or LPS (TLR4 ligand) reverted their suppressive properties to induce T cell immunity. Importantly, P3C stimulation caused functional maturation of Ag-presenting LSECs and enabled them to activate virus-specific CD8+ T cells. The LSEC-mediated CD8+ T cell immunity was initiated by soluble mediators, one of which was IL-12 secreted at a low but sustained level after P3C stimulation. P3C stimulation did not induce programmed death ligand 1 expression on LSECs, thereby favoring T cell proliferation and activation instead of suppression. Our data suggest that LSECs undergo maturation exclusively in response to TLR1/2 ligand stimulation and that the immunological status of LSECs was dependent upon the balance between programmed death ligand 1 and IL-12 expression. These results have implications for our understanding of liver-specific tolerance and autoimmunity and for the development of strategies to overcome T cell tolerance in situations such as chronic viral liver infections or liver cancer.

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Section: Discussionsupporting

confidence: 65%

TLR1/2 Ligand–Stimulated Mouse Liver Endothelial Cells Secrete IL-12 and Trigger CD8+ T Cell Immunity In Vitro

Liu

Jiang

et al. 2013

The Journal of Immunology

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“…In previous studies our laboratory has demonstrated that immunization with B7-H1 deficient dendritic cells or immunization with dendritic cells in combination with B7-H1 blockade induced strong CD8 + T cell responses capable of rejecting established tumors [14]. These results suggest that in the absence of B7-H1 signaling, dendritic cells are able to prime an enhanced CD8 + T cell response.…”

Section: Resultsmentioning

confidence: 82%

“…B7-H1 is known to interact with both PD-1 and CD80 on CD8 + T cells, and signaling downstream of both receptors for B7-H1 has been shown in several models to negatively regulate TCR signaling [10–13]. Expression of B7-H1 by dendritic cells is up regulated upon TLR-dependent activation, thus tempering the stimulatory capability of activated dendritic cells [14]. Much is known about the influence of B7-H1 signaling through PD-1 during the effector phase of an immune response for the induction of an exhausted phenotype in activated CD8 + T cells [15].…”

Section: Introductionmentioning

confidence: 99%

B7-H1 signaling is integrated during CD8+ T cell priming and restrains effector differentiation

Gibbons

Liu

Harrington

et al. 2014

Cancer Immunol Immunother

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A promising strategy in tumor immunotherapy is the use of activated dendritic cells as vehicles for tumor vaccines with the goal of activating anti-tumor T cell responses. Current formulations for dendritic cell-based immunotherapies have limited effects on patient survival, providing motivation for further investigation of ways to enhance dendritic cell priming of anti-tumor T cell responses. Using a brief in vitro priming model, we have found that B7-H1 expressed by activated dendritic cells is integrated during priming of naïve CD8+ T cells and functions to limit the differentiation of effector T cell responses. CD8+ T cells primed by B7-H1 deficient dendritic cells exhibit increased production of IFN-γ, enhanced target-cell killing, and improved anti-tumor activity. Additionally, enhanced memory populations arise from CD8+ T cells primed by B7-H1 deficient dendritic cells. Based on these findings we suggest that early blockade of B7-H1 signaling should be investigated as a strategy to improve dendritic cell-based anti-tumor immunotherapy.

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“…Failure of the immune system to detect and reject transformed cells may lead to tumor development, and tumors can use multiple mechanisms to escape immune-mediated rejection (Wintterle et al, 2003;He et al, 2005;Okazaki and Honjo, 2007). B7-H1 is a newly discovered costimulatory molecule that is closely related to tumor immune escape; it has been found to be overexpressed on a variety of tumor cell surfaces (Liu et al, 2003;Pulko et al, 2009). B7-H1 expression was detected on the cell membrane and in the cytoplasm of bladder cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Association between B7-H1 expression and bladder cancer: a meta-analysis

2015

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ABSTRACT. B7 homolog 1 (B7-H1), which is also known as programmed death-L1, is an important member of the B7/CD28 costimulatory factor superfamily, which are emerging as important mediators of various host immune responses. B7-H1 is differentially expressed in various cell subsets and to different extents in human and murine cells. Human B7-H1 is constitutively expressed at low levels in dendritic cells and activated T cells (compared with high expression in activated murine T cells) and is highly expressed in monocytes and tumor cells. We conducted a meta-analysis to explore the association between B7-H1 expression and bladder cancer risk. Two groups were examined, including 352 bladder cancer cases and 60 healthy controls. Metaanalysis results revealed that B7-H1 expression is positively associated with bladder cancer and is strongly associated with the clinical stage of bladder cancer. However, no significant difference was found with respect to gender and the pathological grade of bladder cancer.

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TLR3-Stimulated Dendritic Cells Up-regulate B7-H1 Expression and Influence the Magnitude of CD8 T Cell Responses to Tumor Vaccination

Cited by 106 publications

References 51 publications

TLR1/2 Ligand–Stimulated Mouse Liver Endothelial Cells Secrete IL-12 and Trigger CD8+ T Cell Immunity In Vitro

TLR1/2 Ligand–Stimulated Mouse Liver Endothelial Cells Secrete IL-12 and Trigger CD8+ T Cell Immunity In Vitro

B7-H1 signaling is integrated during CD8+ T cell priming and restrains effector differentiation

Association between B7-H1 expression and bladder cancer: a meta-analysis

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