Genes that Distinguish Physiological and Pathological Angiogenesis

Seaman, Steven; Stevens, Jarrad; Yang, Mi Young; Logsdon, Daniel; Graff-Cherry, Cari; Croix, Brad St.

doi:10.1016/j.ccr.2007.04.017

Cited by 375 publications

(338 citation statements)

References 51 publications

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“…In addition, antigen-independent anti-CD137 mAb effects have been described for memory T cells, and CD137 seems to be an important player in the differentiation of memory cells [8][9][10]. CD137 can also be expressed by activated NK cells [11], myeloid leukocytes [12] including DC [13,14], and tumor endothelial cells [15]. However, the role of CD137 molecules expressed on these non-T cells during tumor immunotherapy remains undefined [13,16].…”

Section: Introductionmentioning

confidence: 99%

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In vivo depletion of DC impairs the anti‐tumor effect of agonistic anti‐CD137 mAb

et al. 2009

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Anti-CD137 mAb are capable of inducing tumor rejection in several syngeneic murine tumor models and are undergoing clinical trials for cancer. The anti-tumor effect involves costimulation of tumor-specific CD8 1 T cells. Whether antigen cross-presenting DC are required for the efficacy of anti-CD137 mAb treatment has never been examined. Here we show that the administration of anti-CD137 mAb eradicates EG7-OVA tumors by a strictly CD8b 1 T-celldependent mechanism that correlates with increased CTL activity. Ex vivo analyses to determine the identity of the draining lymph node cell type responsible for tumor antigen crosspresentation revealed that CD11c 1 cells, most likely DC, are the main players in this tumor model. A minute number of tumor cells, revealed by the presence of OVA cDNA, reach tumordraining lymph nodes. Direct antigen presentation by tumor cells themselves also participates in anti-OVA CTL induction. Using CD11c diphtheria toxin receptor-green fluorescent protein-C57BL/6 BM chimeric mice, which allow for sustained ablation of DC with diphtheria toxin, we confirmed the involvement of DC in tumor antigen cross-presentation in CTL induction against OVA [257][258][259][260][261][262][263][264] epitope and in the antitumor efficacy induced by anti-CD137 mAb.Key words: CD137 (4-1BB) . Cross-priming . CTL . DC . Tumor immunity Supporting Information available online Introduction CD137, also known as 4-1BB, is a TNF-receptor family costimulatory molecule originally identified on activated T cells [1]. Its natural ligand CD137L is found on APC, including B cells, macrophages, and DC [2]. In the presence of TCR engagement, signaling through CD137 leads to increased T-cell proliferation, cytokine production, and prolonged CD8 1 T-cell survival in vitro [2]. Administration of agonistic anti-CD137 mAb either alone or following peptide vaccination is capable of inducing the eradication of established tumors in several transplantable tumor models [3,4]. This anti-tumor effect is dependent on CD8 1 T cells that show increases in tumor-specific cytotoxic activity and associated IFN-g production [3,4]. Recent studies have demonstrated that the activity of anti-CD137 mAb treatment is also dependent on their ability to enhance the survival of CD8 1 CTL, and on the prevention/reversal of established anergy [5][6][7]. In addition, antigen-independent anti-CD137 mAb effects have been described for memory T cells, and CD137 seems to be an Ã These authors contributed equally to this work.ÃÃ These authors share equal senior authorship. 2424important player in the differentiation of memory cells [8][9][10]. CD137 can also be expressed by activated NK cells [11], myeloid leukocytes [12] including DC [13,14], and tumor endothelial cells [15]. However, the role of CD137 molecules expressed on these non-T cells during tumor immunotherapy remains undefined [13,16].As naïve CTL do not express CD137 on their surface, susceptibility to CD137 triggering depends on prior up-regulation of this receptor [5]. This requires antigen rec...

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Section: Introductionmentioning

confidence: 99%

“…CD137 can also be expressed by activated NK cells [11], myeloid leukocytes [12] including DC [13,14], and tumor endothelial cells [15]. However, the role of CD137 molecules expressed on these non-T cells during tumor immunotherapy remains undefined [13,16].…”

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confidence: 99%

In vivo depletion of DC impairs the anti‐tumor effect of agonistic anti‐CD137 mAb

et al. 2009

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“…3 It is of particular interest that several markers have been characterized that show a specific expression in tumor-associated endothelial cells, but not in normal endothelial cells. 2,4,5 One such molecule, that shows high expression in the tumor-associated neovasculature is prostate-specific membrane antigen (PSMA, also known as folate hydrolase 1, FOLH1). PSMA is a metallo-protease that was originally cloned from human prostate carcinoma cells and has been shown to be overexpressed in the vast majority of prostate cancers.…”

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confidence: 99%

High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity

et al. 2012

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Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in prostate cancer as well as in the neo-vasculature of nonprostatic solid tumors. Here, we determined the expression pattern of PSMA in the vasculature of oral squamous cell carcinoma. Using a previously validated antibody, PSMA staining distribution and cyclooxygenase 2 (COX2) expression status was evaluated in a cohort of patients with squamous cell carcinoma of the oral cavity (n ¼ 96) using immunohistochemistry and was correlated with clinicopathological features as well as outcome. Twenty-four (25%) cases showed no detectable PSMA staining, 48 (50%) demonstrated positive immunoreactivity for PSMA in less than 50% of microvessels and 24 (25%) cases showed strong endothelial PSMA expression in more than 50% of tumor-associated microvessels. High endothelial PSMA expression was associated with greatly reduced survival (18.2 vs 77.3 months; P ¼ 0.0001) and maintained prognostic significance after adjusting for grade and stage in multivariate analysis (hazard ratio ¼ 2.19, P ¼ 0.007). Furthermore, we observed a strong association between endothelial PSMA and cancer cell-specific COX2 expression. In conclusion, we provide the first evidence for the prognostic significance of endothelial PSMA expression in oral squamous cell carcinoma and, suggest a potential interaction between arachidonic acid metabolites and endothelial PSMA expression in the tumor neo-vasculature.

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“…While CD146 has been found to be widely expressed in adult normal vascular endothelium through gene expression profiling and using various anti-CD146 antibodies, for example the s-Endo-1 or the P1H12 antibodies, the AA98 mouse anti-human CD146 antibody developed in Yan's laboratory appears to preferentially label CD146 on tumor-associated endothelium compared to normal endothelium [9,10]. AA98, which binds the same region of CD146 as netrin-1, prevents dimerization of the receptor [7,11].…”

mentioning

confidence: 99%

CD146: the unveiling of a pro-angiogenic netrin receptor

Croix

2015

Cell Res

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Genes that Distinguish Physiological and Pathological Angiogenesis

Cited by 375 publications

References 51 publications

In vivo depletion of DC impairs the anti‐tumor effect of agonistic anti‐CD137 mAb

In vivo depletion of DC impairs the anti‐tumor effect of agonistic anti‐CD137 mAb

High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity

CD146: the unveiling of a pro-angiogenic netrin receptor

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