T cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-beta.

Wrann, Michael; Bodmer, Stefan; Martin, Rainer de; Siepl, Christine; Hofer‐Warbinek, Renate; Frei, Karl; Hofer, Erhard; Fontana, Adriano

doi:10.1002/j.1460-2075.1987.tb02411.x

Cited by 318 publications

(121 citation statements)

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“…4, C, G, and K). Expression of TGF␤ is a known mechanism by which tumors evade immune recognition (24).…”

Section: Muc1 Is Aberrantly Glycosylated In Pancreatic Tumors In Met mentioning

confidence: 99%

“…Other important escape mechanisms are secretion of immunosuppressive substances or induction of suppressor cells or cells secreting inhibitory cytokines in the host immune system and killing of the effector T cells by tumor cells. Factors implicated in this effect include TGF␤ (24). It has been shown previously that TGF␤ may alter TCR subcomponent composition and down-regulate CD3 , ␥, and ␦ but not ⑀, thereby reducing T cell signaling and CTL responses against tumor cells.…”

Section: Figurementioning

confidence: 99%

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Mice with Spontaneous Pancreatic Cancer Naturally Develop MUC-1-Specific CTLs That Eradicate Tumors When Adoptively Transferred

Mukherjee

Ginardi

Madsen

et al. 2000

The Journal of Immunology

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Pancreatic cancer is a highly aggressive, treatment refractory cancer and is the fourth leading cause of death in the United States. In humans, 90% of pancreatic adenocarcinomas overexpress altered forms of a tumor-specific Ag, mucin 1 (MUC1; an epithelial mucin glycoprotein), which is a potential target for immunotherapy. We have established a clinically relevant animal model for pancreatic cancer by developing a double transgenic mouse model (called MET) that expresses human MUC1 as self molecule and develops spontaneous tumors of the pancreas. These mice exhibit acinar cell dysplasia at birth, which progresses to microadenomas and acinar cell carcinomas. The tumors express large amounts of underglycosylated MUC1 similar to humans. Tumor-bearing MET mice develop low affinity MUC1-specific CTLs that have no effect on the spontaneously occurring pancreatic tumors in vivo. However, adoptive transfer of these CTLs was able to completely eradicate MUC1-expressing injectable tumors in MUC1 transgenic mice, and these mice developed long-term immunity. These CTLs were MHC class I restricted and recognized peptide epitopes in the immunodominant tandem repeat region of MUC1. The MET mice appropriately mimic the human condition and are an excellent model with which to elucidate the native immune responses that develop during tumor progression and to develop effective antitumor vaccine strategies.

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“…4, C, G, and K). Expression of TGF␤ is a known mechanism by which tumors evade immune recognition (24).…”

Section: Muc1 Is Aberrantly Glycosylated In Pancreatic Tumors In Met mentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Mice with Spontaneous Pancreatic Cancer Naturally Develop MUC-1-Specific CTLs That Eradicate Tumors When Adoptively Transferred

Mukherjee

Ginardi

Madsen

et al. 2000

The Journal of Immunology

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“…Gliomas have been shown to result in reduced peripheral T-cell responses [2], down-modulated function of circulating APC [3] and particularly to suppressed maturation of peripheral DC [4]. In addition, the localization of the glioma within the immune-privileged CNS, combined with the production of tumorderived immunosuppressive molecules including TGF-b [5][6][7], IL-10 [8], VEGF [9] and prostaglandins [10], is suggested to account for the absence of a successful anti-tumor immune response. As a consequence, glioma patients fail to generate an effective immune response against the intracranially growing tumors.…”

Section: Introductionmentioning

confidence: 99%

“…6E and F). TGF-b1 and TGF-b2 have pleiotropic functions (for review see [46]) and have been described to be expressed very strongly by glioma cells [5][6][7]. The importance of TGF-b in supporting glioma growth is attested by experiments blocking TGF-b production, which positively influence the survival of rats with established gliomas [47].…”

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confidence: 99%

Site‐specific anti‐tumor immunity: Differences in DC function, TGF‐β production and numbers of intratumoral Foxp3⁺ Treg

et al. 2009

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Gliomas localized within the CNS are generally not rejected by the immune system despite being immunogenic. This failure of the immune system has been associated both with glioma-derived immunosuppressive molecules and the immune-privileged state of the CNS. However, the relative contribution of tumor location to the glioma-mediated immunosuppression, as well as the immune mechanisms involved in the failure of glioma rejection are not fully defined. We report here that syngeneic GL261 gliomas growing either intracranially or subcutaneously in mice are infiltrated by DC and T cells. However, only subcutaneous gliomas elicit an effective anti-tumor immune response. In contrast to DC infiltrating subcutaneously grown GL261 gliomas, tumor-infiltrating DC from intracranial gliomas do not activate antigen-dependent T-cell proliferation in vitro. In addition, brain-localized GL261 gliomas are characterized by significantly higher numbers of Foxp3 1 Treg and higher levels of TGF-b1 mRNA and protein expression when compared with GL261 gliomas in the skin. Our data show that gliomas in the CNS, but not in the skin, give rise to TGF-b production and accumulation of both Treg and functionally impaired DC. Thus, not the tumor itself, but its location dictates the efficiency of the antitumor immune response.Key words: DC . Immune privilege . Treg . Tumor immunity Supporting Information available online IntroductionMalignant gliomas, especially the most frequent and aggressive form known as glioblastoma multiforme, are among the most fatal types of tumors. The best standard of care for glioblastoma multiforme, consisting of surgery followed by radiotherapy and chemotherapy with temozolomide, is associated with a median overall survival of 14.6 months following diagnosis [1]. Gliomas have been shown to result in reduced peripheral T-cell responses [2], down-modulated function of circulating APC [3] and particularly to suppressed maturation of peripheral DC [4]. In addition, the localization of the glioma within the immune-privileged CNS, combined with the production of tumorderived immunosuppressive molecules including , , VEGF [9] and prostaglandins [10], is suggested to account for the absence of a successful anti-tumor immune Ã These authors contributed equally to this work. response. As a consequence, glioma patients fail to generate an effective immune response against the intracranially growing tumors. Although it occurs rarely, gliomas are able to metastasize to locations outside of the brain [11]. The low frequency of peripheral glioma metastases might be due to an efficient recognition of tumor cells outside of the CNS. Gliomas express tumor-associated antigens such as ER-2, gp100, and MAGE-1, which can be recognized by cytotoxic T lymphocyte clones [12]. Furthermore, T-cell clonal expansion has been detected in glioma patients [13] and vaccination of patients with autologous tumor lysate-pulsed DC or autologous tumor peptide-pulsed DC [14] can elicit tumor-specific T-cell responses and infiltration of cytotoxic and me...

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“…autocrine growth and hypercalcaemia in adult T-cell leukaemia (Niitsu et al. 1988) and immunosuppression in glioblastoma (Wrann et al. 1987).…”

Section: Identification Of Tgf-pi Activator Released Bk Ka To-iii Cellsmentioning

confidence: 99%

Identification of a transforming growth factor beta-1 activator derived from a human gastric cancer cell line

Horimoto

Kato²,

Takimoto³

et al. 1995

Br J Cancer

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Summarv It has been shown that some types of tumour cells produce actixated transforming grou-th factor beta-i (TGF-I1). How-ever. the mechanism for the actix-ation of TGF-i1 denived from tumour cells has not been fullv elucidated The present study w-as undertaken to characterise an activator of latent TGF-i1 secreted from a human gastric cancer cell line. KATO-I11 Western blot analyses using antibodies for TGF-pI. latency associated peptide (LAP) and latent TGF-0l-binding protein (LTBP) Kevwords: transforming 2rox-th factor beta-I. transforming Trowth factor beta-I activator: eastnc cancer

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T cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-beta.

Cited by 318 publications

References 24 publications

Mice with Spontaneous Pancreatic Cancer Naturally Develop MUC-1-Specific CTLs That Eradicate Tumors When Adoptively Transferred

Mice with Spontaneous Pancreatic Cancer Naturally Develop MUC-1-Specific CTLs That Eradicate Tumors When Adoptively Transferred

Site‐specific anti‐tumor immunity: Differences in DC function, TGF‐β production and numbers of intratumoral Foxp3⁺ Treg

Identification of a transforming growth factor beta-1 activator derived from a human gastric cancer cell line

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T cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-beta.

Cited by 318 publications

References 24 publications

Mice with Spontaneous Pancreatic Cancer Naturally Develop MUC-1-Specific CTLs That Eradicate Tumors When Adoptively Transferred

Mice with Spontaneous Pancreatic Cancer Naturally Develop MUC-1-Specific CTLs That Eradicate Tumors When Adoptively Transferred

Site‐specific anti‐tumor immunity: Differences in DC function, TGF‐β production and numbers of intratumoral Foxp3+ Treg

Identification of a transforming growth factor beta-1 activator derived from a human gastric cancer cell line

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Site‐specific anti‐tumor immunity: Differences in DC function, TGF‐β production and numbers of intratumoral Foxp3⁺ Treg