TRAIL/DR5 Plays a Critical Role in NK Cell-Mediated Negative Regulation of Dendritic Cell Cross-Priming of T Cells

Iyori, Mitsuhiro; Zhang, Tong; Pantel, Haddon; Gagne, Bethany A.; Sentman, Charles L.

doi:10.4049/jimmunol.1003879

Cited by 27 publications

(20 citation statements)

References 49 publications

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“…Although IL-6 may stimulate NK-cell-mediated killing of cancer cells, IL-6 is also known as an autocrine stimulator of cervical neoplastic cell growth [35]. IL- Fig.…”

Section: Discussionmentioning

confidence: 99%

Zerumbone inhibits interleukin-6 and induces apoptosis and cell cycle arrest in ovarian and cervical cancer cells

Abdelwahab

Abdul

Zain

et al. 2012

International Immunopharmacology

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“…Although IL-6 may stimulate NK-cell-mediated killing of cancer cells, IL-6 is also known as an autocrine stimulator of cervical neoplastic cell growth [35]. IL- Fig.…”

Section: Discussionmentioning

confidence: 99%

Zerumbone inhibits interleukin-6 and induces apoptosis and cell cycle arrest in ovarian and cervical cancer cells

Abdelwahab

Abdul

Zain

et al. 2012

International Immunopharmacology

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“…In addition, some articles suggest that these cytokines and cytokine receptors can modulate the tumor microenvironment promoting the pathogenesis of cancer. [40][41][42][43][44] Therefore, for CC patients in the high-risk group these genes may reflect a changing TIME, which may contribute to CC progression and a poorer prognosis. There were significant differences in survival curves between patients with high-risk and low-risk scores.…”

Section: The Prognostic Value Of This Signaturementioning

confidence: 99%

Identification of a prognostic immune signature for cervical cancer to predict survival and response to immune checkpoint inhibitors

et al. 2019

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2019) Identification of a prognostic immune signature for cervical cancer to predict survival and response to immune checkpoint inhibitors, OncoImmunology, 8:12, e1659094, ABSTRACT Cervical cancer (CC) is a leading cause of cancer-related death in women. Limited studies have investigated whether immune-related genes (IRGs) or tumor immune microenvironment (TIME) could be indicators for CC prognoses. The aim of this study was to develop an improved prognostic signature for CC based on IRGs or TIME to predict survival and response to immune checkpoint inhibitors (ICIs). A prognostic signature was constructed using bioinformatics method and its predictive capability was validated. The mechanisms underlying the signature's predictive capability were explored with CIBERSORT algorithm and mutation analysis. Immunophenoscore (IPS) is validated for ICIs response, and was therefore explored in relation to the signature. A prognostic signature based on 11 IRGs was developed. A multivariate analysis revealed that the 11-IRG signature was an independent prognostic factor for overall survival (OS) and progression-free interval in CC patients. In the 11-IRG signature highrisk group, CD8 T cells and resting mast cells, which are found to associate with better OS in our study, were lower; activated mast cells, associated with poorer OS, were higher, compared with the low-risk group. An IPS analysis suggested that the 11-IRG signature low-risk group, which possessed a higher IPS, represented a more immunogenic phenotype that was more inclined to respond to ICIs. In short, an 11-IRG prognostic signature for predicting CC patients' survival and response to ICIs was firmly established. The predictive capability of this model in CC requires further testing with the goal of better prognostic stratification and treatment management. ARTICLE HISTORY

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“…Mechanistically, TRAIL + T cells appear to inhibit the proliferation of other alloreactive T cells. While a body of evidence suggests a role for the TRAIL/DR5 pathway in immune regulation (15,20), its physiological role in suppressing GVHD has not been clear (11). We found that TRAIL receptor DR5 expression is induced in APCs postirradiation and that GVHD suppression by TRAIL + T cells is less effective in DR5 KO recipients, suggesting that DR5 expression (possibly on host APCs) could play a role in GVHD suppression by TRAIL + T cells.…”

Section: Discussionmentioning

confidence: 56%

Adoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity

Ghosh¹,

Dogan²,

Moroz³

et al. 2013

J. Clin. Invest.

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Current strategies to suppress graft-versus-host disease (GVHD) also compromise graft-versus-tumor (GVT)responses. Furthermore, most experimental strategies to separate GVHD and GVT responses merely spare GVT function without actually enhancing it. We have previously shown that endogenously expressed TNF-related apoptosis-inducing ligand (TRAIL) is required for optimal GVT activity against certain malignancies in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In order to model a donor-derived cellular therapy, we genetically engineered T cells to overexpress TRAIL and adoptively transferred donor-type unsorted TRAIL + T cells into mouse models of allo-HSCT. We found that murine TRAIL + T cells induced apoptosis of alloreactive T cells, thereby reducing GVHD in a DR5-dependent manner. Furthermore, murine TRAIL + T cells mediated enhanced in vitro and in vivo antilymphoma GVT response. Moreover, human TRAIL + T cells mediated enhanced in vitro cytotoxicity against both human leukemia cell lines and against freshly isolated chronic lymphocytic leukemia (CLL) cells. Finally, as a model of off-the-shelf, donor-unrestricted antitumor cellular therapy, in vitro-generated TRAIL + precursor T cells from third-party donors also mediated enhanced GVT response in the absence of GVHD. These data indicate that TRAIL-overexpressing donor T cells could potentially enhance the curative potential of allo-HSCT by increasing GVT response and suppressing GVHD.

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TRAIL/DR5 Plays a Critical Role in NK Cell-Mediated Negative Regulation of Dendritic Cell Cross-Priming of T Cells

Cited by 27 publications

References 49 publications

Zerumbone inhibits interleukin-6 and induces apoptosis and cell cycle arrest in ovarian and cervical cancer cells

Zerumbone inhibits interleukin-6 and induces apoptosis and cell cycle arrest in ovarian and cervical cancer cells

Identification of a prognostic immune signature for cervical cancer to predict survival and response to immune checkpoint inhibitors

Adoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity

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