The Lymphotoxin-β Receptor Is Necessary and Sufficient for LIGHT-mediated Apoptosis of Tumor Cells

Rooney, Isabelle; Butrovich, Kris D.; Glass, Alison A.; Borboroglu, Stephen; Benedict, Chris A.; Whitbeck, J. Charles; Cohen, Gary H.; Eisenberg, Roselyn J.; Ware, Carl F.

doi:10.1074/jbc.275.19.14307

Cited by 210 publications

(216 citation statements)

References 52 publications

(44 reference statements)

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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%

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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%

“…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].…”

Section: Introductionmentioning

confidence: 99%

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Yü¹,

Fu²

2008

Cytokine & Growth Factor Reviews

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“…Functionally, LIGHT can induce apoptosis of some tumor cells in vitro [13], via lymphotoxin g receptor triggering [14], and in vivo [11]. Decoy receptor 3 (DcR3, TR6), a soluble receptor for LIGHT, inhibits LIGHT-mediated apoptosis [15] and can presumably modulate other LIGHT functions.…”

Section: Introductionmentioning

confidence: 99%

LIGHT, a new TNF superfamily member, is essential for memory T helper cell‐mediated activation of dendritic cells

et al. 2003

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LIGHT is a recently identified member of the TNF superfamily that is up-regulated on activated T cells and can cooperate with CD40L to condition DC for the priming of CTL. In this report, we show that an intracellular pool of LIGHT is found selectively in some CD45RA -CD27 + CD4 + "central" memory T cells and to a greater extent in some CD45RA -CD27 -CD4 + effector memory T cells. LIGHT, like CD40L, is rapidly up-regulated on memory CD4 + T cells upon activation. Unlike CD40L, LIGHT up-regulation on naive T cells is delayed. Stimulation of DC with each subset of memory T cells in the presence of superantigen revealed that CD40L and LIGHT are required for optimal secretion of IL-12. Moreover, effector memory T cells, which can interact with DC in peripheral tissues, contribute to CCR7 induction on DC. LIGHT and CD40L can also regulate IL-12 production by CCR7 + DC capable of migration to lymph nodes. These data suggest that both LIGHT and CD40L may be involved in the maintenance or reactivation of secondary Th1 responses.

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“…CD40 was first functionally characterised in B cells Recruitment of TRAF2 and TRAF3 through LTβR signalling was found to be important with TRAF3 being critical in apoptosis (65,70), but JNK activation in this context has not been reported. Moreover, two studies demonstrated that TRAF3 knockdown leads to the increase of protein expression of noncanonical pathway NF-B members, e.g.…”

Section: Cd40 and Its Signalling And Functional Similarities To Lt Inmentioning

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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The Lymphotoxin-β Receptor Is Necessary and Sufficient for LIGHT-mediated Apoptosis of Tumor Cells

Cited by 210 publications

References 52 publications

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Targeting tumors with LIGHT to generate metastasis-clearing immunity

LIGHT, a new TNF superfamily member, is essential for memory T helper cell‐mediated activation of dendritic cells

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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