Targeting tumors with LIGHT to generate metastasis-clearing immunity

Yü, Ping; Fu, Yang–Xin

doi:10.1016/j.cytogfr.2008.04.004

Cited by 53 publications

(49 citation statements)

References 97 publications

(124 reference statements)

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“…Indeed, earlier studies indicated that LIGHT can promote dendritic cell expansion and maturation, especially when in cooperation with CD40L (29,30). Second, LIGHT can induce the expression of chemokines by stromal cells to attract T cells migrating into the tumors (31). Third, LIGHT can promote Teff expansion and differentiation, even in a Treg-enriched environment, as we have shown in this paper.…”

Section: Discussionsupporting

confidence: 51%

Promoting Immune Responses by LIGHT in the Face of Abundant Regulatory T Cell Inhibition

Wang

Zhu

Yü³

et al. 2009

The Journal of Immunology

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CD4+ regulatory T cell (Treg) populations are believed to play very important roles in the suppression of immune responses. Overriding Treg inhibition is necessary for initiating primary immune reaction upon inflammatory Ag stimulation. LIGHT, TNF superfamily member 14, has been shown to be a costimulatory molecule for effector T cells. Overexpression of lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) on T cells induces strong T cell-mediated experimental intestinal inflammation. How this process is initiated by LIGHT in suppressive intestinal environments remains incompletely understood. In this study, we assessed the effect of LIGHT on Tregs. Our results indicate that LIGHT can support the expansion and function of Tregs. However, when LIGHT was highly expressed, these abundant Tregs failed to suppress the development of T cell-mediated experimental colitis and antitumor immunity. We showed that this might be, in part, due to an ability of LIGHT to promote effector T cell proliferation and differentiation even in a Treg-abundant environment. Our data collectively suggest that LIGHT might be a critical cytokine involved in the development of autoimmune inflammatory diseases and that LIGHT-targeted immunotherapy might be useful in the treatment of these diseases.

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Section: Discussionsupporting

confidence: 51%

Promoting Immune Responses by LIGHT in the Face of Abundant Regulatory T Cell Inhibition

Wang

Zhu

Yü³

et al. 2009

The Journal of Immunology

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“…Constitutive expression of LIGHT can enhance the extravasation and homing of naive T cells (19,20). Moreover, recent data further confirmed the role of LIGHT in priming potent antitumor immunity (17,(21)(22)(23)(24)(25). For instance, we have showed that forced expression of LIGHT in the tumor could induce a massive infiltration of naive T cells into tumor tissues.…”

Section: Introductionmentioning

confidence: 51%

“…Our previous data have shown that LIGHT could prime potent antitumor immunity (22,24,25). To determine whether expression of LIGHT on MSCs still possesses potent antitumor immunity, we first carried out the experiments with nude mice.…”

Section: Immune Activation By Msc-l Contributes To Tumor Regressionmentioning

confidence: 99%

LIGHT Delivery to Tumors by Mesenchymal Stem Cells Mobilizes an Effective Antitumor Immune Response

Zou

Zheng

et al. 2012

Cancer Research

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Bone marrow-derived mesenchymal stem cells (MSC) have been shown to home into tumor tissues, where they promote tumor growth and suppress immune rejection. In this study, we tested whether MSCs engineered to express the immune stimulating factor LIGHT, a member of the TNF superfamily, could induce tumor regression. Using in vitro and in vivo migration assays, we found that LIGHT-expressing MSCs (MSC-L) displayed a strong tropism for tumor tissues. MSC-L treatment activated the LIGHT-signaling pathway, effectively organizing a potent antitumor immune response that stimulated an influx of T cells and inhibited tumor growth in vivo. CD4 T cells were found to play a role in the induction phase of the immune response, and CD8 T cells were shown to be essential for the effector phase. Together, our findings indicate that MSCs can effectively home into and deliver immune stimulating molecules to tumor tissues, thereby reversing the immune-suppressive environment, promoting antitumor immunity, and inhibiting tumor growth. Cancer Res; 72(12); 2980-9. Ó2012 AACR.

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“…The relative location of CTLs to TLS may be important for CTLs receiving help from T helper cells for generation of an effective and durable antitumor immune response. Interestingly, it has been reported that LIGHT, a TNF superfamily member and a ligand for the lymphotoxin b receptor, facilitates the generation of TLS (39,40) and recruits na€ ve T cells into the tumor (41). Expression of LIGHT in tumors has been shown to enhance chemokine secretion within the tumor, favoring the infiltration and expansion of functional CD8 þ T cells (42).…”

Section: Anatomical Locationmentioning

confidence: 99%

Trafficking of T Cells into Tumors

2014

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T cells are a crucial component of the immune response to infection and cancer. In addition to coordinating immunity in lymphoid tissue, T cells play a vital role at the disease site, which relies on their efficient and specific trafficking capabilities. The process of T-cell trafficking is highly dynamic, involving a series of distinct processes, which include rolling, adhesion, extravasation, and chemotaxis. Trafficking of T cells to the tumor microenvironment is critical for the success of cancer immunotherapies such as adoptive cellular transfer. Although this approach has achieved some remarkable responses in patients with advanced melanoma and hematologic malignancy, the success against solid cancers has been more moderate. One of the major challenges for adoptive immunotherapy is to be able to effectively target a higher frequency of T cells to the tumor microenvironment, overcoming hurdles associated with immunosuppression and aberrant vasculature. This review summarizes recent advances in our understanding of T-cell migration in solid cancer and immunotherapy based on the adoptive transfer of natural or genetically engineered tumor-specific T cells and discusses new strategies that may enhance the trafficking of these cells, leading to effective eradication of solid cancer and metastases. Cancer Res; 74(24); 7168-74. Ó2014 AACR.

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Targeting tumors with LIGHT to generate metastasis-clearing immunity

Cited by 53 publications

References 97 publications

Promoting Immune Responses by LIGHT in the Face of Abundant Regulatory T Cell Inhibition

Promoting Immune Responses by LIGHT in the Face of Abundant Regulatory T Cell Inhibition

LIGHT Delivery to Tumors by Mesenchymal Stem Cells Mobilizes an Effective Antitumor Immune Response

Trafficking of T Cells into Tumors

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