Transforming Growth Factor Beta 1 is Significantly Elevated in Plasma of Patients Suffering From Renal Cell Carcinoma

Junker, U.; Knoefel, B.; Nuske, K.; Rebstock, K.; Steiner, Thomas; Wunderlich, Heiko; Junker, Kerstin; Reinhold, Dirk

doi:10.1016/s0022-5347(01)63911-9

Cited by 14 publications

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“…This is in line with recent work showing that soluble factor(s), produced by AML cells, impede the phosphorylation of the retinoblastoma protein (pRb) by cyclin D ‐cdk6/4 which then blocks the transition of cells from G0 to G1 [21]. The immunosuppressive cytokine TGF‐ β [29], secreted by solid tumours [30] and some forms of leukaemia [38], blocks cell proliferation by increasing the expression of mitotic inhibitory proteins that arrest cell division [32]. Our data, however, rule this out as a mode of operation for AML induced immunosuppression.…”

Section: Discussionsupporting

confidence: 82%

“…In order to evade immune detection, solid tumours can secrete soluble factors inducing apoptosis in T cells [26–28] or simply arresting cell division [29–32]. We therefore initially investigated the possibility that HL60 AML cell line supernatant was inhibiting lymphocyte proliferation by inducing apoptosis.…”

Section: Resultsmentioning

confidence: 99%

“…Propidium iodide staining of lymphocyte cell nuclei after a 72‐h exposure to HL60 supernatant showed no evidence of apoptosis (data not shown). HL60 AML cell line supernatant was also tested, by ELISA, for the presence of IL‐10 [33–35] and TGF‐ β [29,30], cytokines that are commonly secreted by solid tumours as a mechanism of immune evasion. Figure 5a shows that both these cytokines are not present in the immunosuppressive supernatant.…”

Section: Resultsmentioning

confidence: 99%

“…Notwithstanding that we are yet to identify the immunosuppressive factor(s) secreted by HL60 cells, we have eliminated two factors commonly secreted by tumours; namely TGF‐ β [29,30] and IL‐10 [33–35]. The observation that T cells exposed to HL60 supernatant did not show an accumulation of p27/Kip 1 mitotic inhibitory protein was confirmatory of the factor(s) involved in this immunosuppression not being TGF‐ β .…”

Section: Discussionmentioning

confidence: 99%

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Acute myeloid leukaemia cells secrete a soluble factor that inhibits T and NK cell proliferation but not cytolytic function – implications for the adoptive immunotherapy of leukaemia

Orleans-Lindsay

Barber

Prentice

et al. 2001

Clinical and Experimental Immunology

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SUMMARYEvidence of an immune mediated graft-versus-leukaemia effect has led to the belief that T and NK cell based adoptive immunotherapy can constitute effective treatment for relapsed leukaemias. However, work on solid tumours has shown this strategy may be hampered, by an immune escape mechanism in which tumour secreted immunosuppressive factors compromise T and NK cell function. Indeed, acute myeloid leukaemia (AML) cells secrete immunosuppressive factors that block the synthesis of Th1 type cytokines in T cells. We demonstrate here that this immunosuppression, mediated by both HL60 AML cell line and primary AML blasts, inhibits T and NK cell proliferation but not cytolytic activity. Supernatants from HL60 cell line and primary AML blasts inhibited T cell proliferation to mitogenic and alloantigen stimulation but had no effect on cytolytic function. Similarly, the proliferation of NK cells to IL-2 and IL-15 stimulation was inhibited whilst their cytolytic function, shown by lysis of AML blasts, K562 and Daudi cells remained unaffected. The failure of T and NK cells to proliferate was not due to effector cell apoptosis. Indeed, removal of lymphocytes from the immunosuppressive environment partially restored their capacity to respond to mitogenic stimulation. T cells exposed to immunosuppressive supernatants did not increase expression of mitotic inhibitory proteins that arrest cell division, thereby ruling this out as a mechanism of operation for this immunosuppression. T cell expansion requires antigen stimulation, usually provided in the form of AML blasts, therefore our data suggest that NK cells may be more practical for the immunotherapy of AML.

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Section: Discussionsupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Acute myeloid leukaemia cells secrete a soluble factor that inhibits T and NK cell proliferation but not cytolytic function – implications for the adoptive immunotherapy of leukaemia

Orleans-Lindsay

Barber

Prentice

et al. 2001

Clinical and Experimental Immunology

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“…The growth inhibitory effect of TGF-b1 was accompanied by both a reduction in MC proliferation and enhancement of MC apoptosis, and appeared in a concentration range similar to TGF-b1 levels found in human plasma. 31 Such TGF-b1 effects have been reported previously for epithelial, endothelial, and haematopoietic cells, including eosinophils and murine MC, in all of which TGF-b1 causes cell cycle arrest. 3 22 Induction of apoptosis by TGF-b1 was also found in human lymphoma cell lines, leukaemia cells, and normal blood eosinophils.…”

Section: Discussionsupporting

confidence: 56%

Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor 1

Gebhardt

Lorentz²,

Detmer³

et al. 2005

Gut

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Background and aims: Transforming growth factor b1 (TGF-b1) is expressed in the healthy human intestine and controls mucosal immune responses and inflammation by regulating the function of lymphocytes, macrophages, dendritic cells, and eosinophils. Here, we asked whether human intestinal mast cells (MC) might also be subject to immunoregulation by TGF-b1. Methods: MC were isolated from the intestinal mucosa, purified, and cultured in vitro in the presence of stem cell factor (SCF) with or without TGF-b1. Growth characteristics, phenotype, and immunological mediator release of MC were analysed by reverse transcription-polymerase chain reaction, flow cytometry, immunocytochemistry, western blot, and different immunoassays, respectively. Results: TGF-b1 dose dependently (ED50 < 0.1 ng/ml) inhibited SCF dependent growth of human intestinal MC by both enhancing apoptosis and decreasing proliferation. In parallel, TGF-b1 increased the percentage of connective tissue-type MC expressing tryptase and chymase while downregulating expression of the receptors for IgE and SCF. Furthermore, TGF-b1 dramatically changed the profile of mediators released by MC following IgE receptor crosslinking. Release of histamine, cysteinyl-leukotrienes, and tumour necrosis factor a was strongly reduced whereas prostaglandin D2 generation and cyclooxygenase 1 and 2 expression were upregulated by TGF-b1. Conclusions: Our data indicate that TGF-b1 acts as a novel potent inhibitor and modulator of human intestinal MC effector functions. The change in MC mediator release profile and protease expression induced by TGF-b1 might be of relevance for the control of MC associated disorders of the intestine such as allergic reactions, Crohn's disease, irritable bowel syndrome, and parasitic infection.

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The detection of renal carcinoma cells in the peripheral blood with an enhanced reverse transcriptase-polymerase chain reaction assay for MN/CA9

McKiernan

Buttyan

Bander

et al. 1999

Cancer

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BACKGROUND Using a reverse transcriptase–polymerase chain reaction (RT‐PCR) assay, the authors previously determined the expression of MN/CA9 mRNA in renal cell carcinoma (RCC) and its absence in benign renal tissue. In the current study, the utility of an enhanced RT‐PCR assay in the detection of renal carcinoma cells in the peripheral blood was assessed. METHODS An enhanced MN/CA9 RT‐PCR assay was applied to peripheral blood samples from a total of 96 patients. Forty‐two patients had renal tumors, including 5 with benign renal lesions, 28 with localized RCC, and 9 with metastatic RCC. Fifty‐four control patients without renal tumors were similarly tested. Pathologic staging for patients with localized cancer was T1N0M0 for 5, T2N0M0 for 9, and T3N0M0 for 14 patients. RESULTS Cells expressing MN/CA9 were detected in 1 of 54 controls (1.8%) and in 18 of 37 cancer patients (49%). Thirteen of twenty eight patients (46%) with localized RCC and 5 of 9 (56%) with metastatic disease tested positive with the assay. No patient with a benign renal tumor exhibited MN/CA9 expression. All blood test results for patients with clear cell RCC were noted to be positive. No correlation was noted between MN/CA9 results and age, gender, or tumor grade. The differences in MN/CA9 results according to T classification were not statistically significant. CONCLUSIONS The enhanced RT‐PCR assay for MN/CA9 is a highly specific technique for detecting circulating renal carcinoma cells in the peripheral blood, and it may prove useful in the diagnosis and monitoring of RCC. Cancer 1999;86:492–7. © 1999 American Cancer Society.

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Transforming Growth Factor Beta 1 is Significantly Elevated in Plasma of Patients Suffering From Renal Cell Carcinoma

Cited by 14 publications

References 0 publications

Acute myeloid leukaemia cells secrete a soluble factor that inhibits T and NK cell proliferation but not cytolytic function – implications for the adoptive immunotherapy of leukaemia

Acute myeloid leukaemia cells secrete a soluble factor that inhibits T and NK cell proliferation but not cytolytic function – implications for the adoptive immunotherapy of leukaemia

Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor 1

The detection of renal carcinoma cells in the peripheral blood with an enhanced reverse transcriptase-polymerase chain reaction assay for MN/CA9

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