Herpesvirus Entry Mediator Ligand (HVEM-L), a Novel Ligand for HVEM/TR2, Stimulates Proliferation of T Cells and Inhibits HT29 Cell Growth

Harrop, Jeremy; McDonnell, Peter; Brigham-Burke, Michael; Lyn, Sally D.; Minton, Jayne A.L.; Tan, K. B.; Dede, Kim; Spampanato, Jay; Silverman, Carol; Hensley, Preston; DiPrinzio, Rocco; Emery, John G.; Deen, Keith C.; Eichman, Christopher; Chabot-Fletcher, Marie; Truneh, Alemseged; Young, Peter R.

doi:10.1074/jbc.273.42.27548

Cited by 223 publications

(227 citation statements)

References 52 publications

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“…For example, apoptosis of cancer cells induced by chemotherapeutic agents or radiation releases antigen, enhancing the cross-priming of T cells [65,66]. LIGHT has been shown to signal via LTβR and/or HVEM expressed on the tumor cells to induce apoptosis of the tumor cells, especially in the presence of interferon-γ [4,5,67]. Using a xenograft tumor model in which human breast cancer cells were inoculated to athymic nude mice, LIGHT directly inhibited tumor growth by causing apoptosis in the absence of T cells [68].…”

Section: Tumor Cell Apoptosis Induced By Light Promotes Immune Recognmentioning

confidence: 99%

“…This might be in part contributed to the ability of LIGHT to act as a strong costimulatory molecule for T cell activation, expansion and cytokine production, possibly by binding to HVEM on T cells [2,3,68]. This was initially demonstrated by experiments in which immobilized recombinant LIGHT promoted T cell proliferation in the presence of anti-CD3 [5]. Reagents that blocked HVEM, like anti-HVEM antibody [6] or HVEM-Ig [83], reduced T cell expansion and their cytokine production in the same setting.…”

Section: Light Sustains Effector T Cell Functions At the Tumor Sitementioning

confidence: 99%

“…LIGHT uniquely binds to two functional receptors, HVEM and lymphotoxin β receptor (LTβR) [2,4], which are TNF receptor superfamily members (TNFRSF) that have distinct expression patterns. HVEM is broadly expressed on hematopoietic cells including T cells, natural killer (NK) cells, and monocytes [5,6]. Conversely, LTβR is mainly expressed on nonhematopoietic cells such as stromal cells [7] and some monocyte cell lines [8].…”

Section: Introductionmentioning

confidence: 99%

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Targeting tumors with LIGHT to generate metastasis-clearing immunity

Yü¹,

Fu²

2008

Cytokine & Growth Factor Reviews

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Metastastic diseases cause the majority of morbidity and mortality of cancer patients. Established tumors form both physical and immunological barriers to limit immune detection and destruction. Current immunotherapy of vaccination and adoptive transfer shows limited effect at least in part due to the existing barriers in the tumors and depending on the knowledge of tumor antigens. Tumor necrosis factor superfamily member 14 (TNFSF14) LIGHT interacts with stromal cells, dendritic cells, NK cells, naïve and activated T cells and tumor cells inside the tumor tissues via its two functional receptors, HVEM and lymphotoxin β receptor (LTβR). Targeting tumor tissues with LIGHT leads to augmentation of priming, recruitment, and retention of effector cells at tumor sites, directly or indirectly, to induce strong anti-tumor immunity to inhibit the growth of primary tumors as well as eradicate metastases. Intratumor treatment would break tumor barriers and allow strong immunity against various tumors without defining tumor antigens. This review summarizes recent findings to support that LIGHT is a promising candidate for an effective cancer immunotherapy.

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Section: Tumor Cell Apoptosis Induced By Light Promotes Immune Recognmentioning

confidence: 99%

Section: Light Sustains Effector T Cell Functions At the Tumor Sitementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeting tumors with LIGHT to generate metastasis-clearing immunity

Yü¹,

Fu²

2008

Cytokine & Growth Factor Reviews

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“…HVEM, initially identified as a herpes virus receptor, regulates T cell proliferation positively or negatively depending on its ligands (Cai and Freeman 2009). HVEM binds to LIGHT, augmenting T cell proliferation and IFN-γ production (Harrop et al 1998;Tamada et al 2000), whereas its binding to BTLA and CD160 negatively regulates T cell proliferation (Cai et al 2008;Sedy et al 2005). ICOS also enhances T cell activation, although it seems to be more important for differentiation of activated T cells (McAdam et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule

Ando

Yasuoka

Mishima

et al. 2013

In Vitro Cell.Dev.Biol.-Animal

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T cell activation is regulated by two distinct signals, signal one and two. Concanavalin A (ConA) is an antigen-independent mitogen and functions as signal one inducer, leading T cells to polyclonal proliferation. CD28 is known to be one of major costimulatory receptors and to provide signal two in the ConA-induced T cell proliferation. Here, we have studied the implication of other costimulatory pathways in the ConA-mediated T cell proliferation by using soluble recombinant proteins consisting of an extracellular domain of costimulatory receptors and Fc portion of human IgG. We found that T cell proliferation induced by ConA, but not PMA plus ionomycin or anti-CD3 mAb, is significantly inhibited by HVEM-Ig, even in the presence of CD28 signaling. Moreover, the high concentration of HVEM-Ig molecules almost completely suppressed ConA-mediated T cell proliferation. These results suggest that HVEM might play more important roles than CD28 in ConA-mediated T cell proliferation.

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“…LIGHT is constitutively expressed on myeloid cells, primary immature DCs and its expression can be induced on the surface of activated T cells and macrophages (79,86,97). LIGHT can ligate both LTβR and HVEM receptors (and can bind to soluble receptor DcR3) to regulate cell proliferation, differentiation and growth inhibition (see below).…”

Section: Lightmentioning

confidence: 99%

Regulation of cell fate by lymphotoxin (LT) receptor signalling: Functional differences and similarities of the LT system to other TNF superfamily (TNFSF) members

Albarbar

Dunnill

Georgopoulos

2015

Cytokine & Growth Factor Reviews

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The role of TNFR family members in regulating cell fate both in the immune system and in non-lymphoid tissues has been under extensive research for decades. Moreover, the ability of several family members (death receptors) to induce death (mainly via apoptosis) represents a promising target for cancer therapy. Many studies have focused mostly on death receptors such as TNFRI, Fas and TRAIL-R due to their strong pro-apoptotic potential.Yet, cell death can be triggered via non-classical death receptors, and the Lymphotoxin (LT) system represents a very good example of such a TNFR subfamily. Here we provide a comprehensive review of intracellular signalling pathways and cellular responses to LTspecific signalling, and compare for the first time the LT system to other TNFRs, such as CD40. Our aim is to highlight that non-classical TNFR-TNFL dyads such as the LT system demonstrate more complex, cell-type and context-specific capabilities. Understanding these complexities will permit a better understanding of the biological mechanisms via which nondeath domain-containing TNFRs induce cell death, but may also allow the design of better therapeutic strategies.

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Herpesvirus Entry Mediator Ligand (HVEM-L), a Novel Ligand for HVEM/TR2, Stimulates Proliferation of T Cells and Inhibits HT29 Cell Growth

Abstract: Herpesvirus entry mediator (HVEM),

Cited by 223 publications

References 52 publications

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule

Regulation of cell fate by lymphotoxin (LT) receptor signalling: Functional differences and similarities of the LT system to other TNF superfamily (TNFSF) members

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