Expression of HLA-DR antigens on tumour cells does not contribute to skin reactivity to autologous cholesteryl hemisuccinate (CHS)-treated tumour cells in patients with metastatic melanoma

1987 ◽  
Vol 24 (3) ◽  
pp. 272-274 ◽  
Author(s):  
Marta Munzarová ◽  
Daniela Zemanová ◽  
Jan Kovařík ◽  
Zdeněk Pačovský ◽  
Aleš Rejthar ◽  
...  
1985 ◽  
Vol 20 (2) ◽  
pp. 179-181 ◽  
Author(s):  
Marta Munzarová ◽  
Daniela Zemanová ◽  
Jan Kovařik ◽  
Aleš Rejthar

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 49 ◽  
Author(s):  
Serena Saladini ◽  
Michele Aventaggiato ◽  
Federica Barreca ◽  
Emanuela Morgante ◽  
Luigi Sansone ◽  
...  

Metformin has been shown to inhibit glutaminase (GLS) activity and ammonia accumulation thereby reducing the risk of hepatic encephalopathy in type 2 diabetic patients. Since tumour cells are addicted to glutamine and often show an overexpression of glutaminase, we hypothesize that the antitumoral mechanism of metformin could be ascribed to inhibition of GLS and reduction of ammonia and ammonia-induced autophagy. Our results show that, in different tumour cell lines, micromolar doses of metformin prevent cell growth by reducing glutamate, ammonia accumulation, autophagy markers such as MAP1LC3B-II and GABARAP as well as degradation of long-lived proteins. Reduced autophagy is then accompanied by increased BECN1/BCL2 binding and apoptotic cell death. Interestingly, GLS-silenced cells reproduce the effect of metformin treatment showing reduced MAP1LC3B-II and GABARAP as well as ammonia accumulation. Since metformin is used as adjuvant drug to increase the efficacy of Cisplatin-based neoadjuvant chemotherapy, we co-treated tumour cells with micromolar doses of metformin in the presence of cisplatin observing a marked reduction of MAP1LC3B-II and an increase of caspase 3 cleavage. In conclusion, our work demonstrates that the anti-tumoral action of metformin is due to the inhibition of glutaminase and autophagy and could be used to improve the efficacy of chemotherapy.


ChemMedChem ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. 1465-1471 ◽  
Author(s):  
Nikolitsa Nomikou ◽  
Christine Sterrett ◽  
Ciara Arthur ◽  
Bridgeen McCaughan ◽  
John F. Callan ◽  
...  

Oncotarget ◽  
2017 ◽  
Vol 8 (40) ◽  
pp. 67355-67368 ◽  
Author(s):  
Carlos A. Aya-Bonilla ◽  
Gabriela Marsavela ◽  
James B. Freeman ◽  
Chris Lomma ◽  
Markus H. Frank ◽  
...  

1984 ◽  
Vol 33 (6) ◽  
pp. 813-819 ◽  
Author(s):  
J. Alero Thomas ◽  
Virginia Iliescu ◽  
Dorothy H. Crawford ◽  
Ridha Ellouz ◽  
Mohamed Cammoun ◽  
...  

2007 ◽  
Vol 25 (18) ◽  
pp. 2546-2553 ◽  
Author(s):  
Paola Filipazzi ◽  
Roberta Valenti ◽  
Veronica Huber ◽  
Lorenzo Pilla ◽  
Paola Canese ◽  
...  

Purpose Phenotypic and functional features of myeloid suppressor cells (MSC), which are known to serve as critical regulators of antitumor T-cell responses in tumor-bearing mice, are still poorly defined in human cancers. Here, we analyzed myeloid subsets with suppressive activity present in peripheral blood of metastatic melanoma patients and evaluated their modulation by a granulocyte-macrophage colony-stimulating factor (GM-CSF) –based antitumor vaccine. Patients and Methods Stage IV metastatic melanoma patients (n = 16) vaccinated with autologous tumor-derived heat shock protein peptide complex gp96 (HSPPC-96) and low-dose GM-CSF provided pre- and post-treatment whole blood specimens. Peripheral-blood mononuclear cells (PBMCs) were analyzed by flow cytometry, separated into cellular subsets, and used for in vitro proliferation assays. PBMCs from stage-matched metastatic melanoma patients (n = 12) treated with non–GM-CSF-based vaccines (ie, HSPPC-96 alone or interferon alfa/melanoma–derived peptides) or sex- and age-matched healthy donors (n = 16) were also analyzed for comparison. Results The lack of or low HLA-DR expression was found to identify a CD14+ cell subset highly suppressive of lymphocyte functions. CD14+HLA-DR–/lo cells were significantly expanded in all metastatic melanoma patients, whereas they were undetectable in healthy donors. Suppressive activity was mediated by transforming growth factor beta (TGF-β), whereas no involvement of the arginase and inducible nitric oxide synthase pathways could be detected. CD14+HLA-DR–/lo cells, as well as spontaneous ex vivo release and plasma levels of TGF-β, were augmented after administration of the HSPPC-96/GM-CSF vaccine. No enhancement of the CD14+-mediated suppressive activity was found in patients receiving non–GM-CSF-based vaccines. Conclusion CD14+HLA-DR–/lo cells exerting TGF-β–mediated immune suppression represent a new subset of MSC potentially expandable by the administration of GM-CSF–based vaccines in metastatic melanoma patients.


2018 ◽  
pp. clincanres.0309.2018 ◽  
Author(s):  
Douglas B. Johnson ◽  
Jennifer M Bordeaux ◽  
Ju-Young Kim ◽  
Christine A Vaupel ◽  
David L. Rimm ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19050-e19050
Author(s):  
Christiane Meyer ◽  
Laurene Cagnon ◽  
Nicole Montandon ◽  
Grégoire Berthod ◽  
Loredana Leyvraz ◽  
...  

e19050 Background: Myeloid derived suppressor cells (MDSC) are key immunosuppressive cells enriched in peripheral blood during chronic inflammation. While these cells have been extensively studied in mice, their human counterparts are less well characterized. Several MDSC populations have been identified in cancer patients, depending on tumor type and experimental settings. MDSC include immature macrophages, granulocytes and dendritic cells, at different degree of maturation, from immature CD33+, to mature CD14+ and CD15+HLA-DR- cells. The goal of this study was to characterize myeloid cells in melanoma patients compared with healthy donors (HD) to identify inflammation-mediated alterations involved in melanoma progression. Methods: PBMC were isolated by Lymphoprep gradient centrifugation from fresh blood samples of patients with malignant melanoma. We performed 9-color FACS staining of the freshly isolated cells. Results: CD15+ granulocytic MDSC are enriched in the mononuclear cell layer after gradient centrifugation, together with the CD14+ monocytic MDSCs. They display significantly different sedimentation abilities compared with neutrophils. Furthermore, CD14 and CD15 were partially co-expressed by the monocytic and granulocytic MDSC subsets, respectively. Our data show that CD14+HLA-DR- monocytic and CD15+HLA-DR- granulocytic MDSC were significantly enriched in peripheral blood of metastatic melanoma patients, regardless of whether or not they received any prior therapy for metastatic melanoma. The more immature CD33+CD11b- subset was found at significantly lower frequencies in melanoma patients compared with HD. We found a trend for accumulation of non-classical CD14+CD16+ monocytes. However, the increased percentages did not differ significantly from HD. The frequencies of classical CD14+CD16- monocytes were unchanged. Conclusions: Melanoma is associated with increased frequencies of CD14+ monocytic and CD15+ granulocytic MDSC, and decreased frequencies of the more immature CD33+CD11b- cells. This finding demonstrates tumor-mediated changes in the composition of myeloid cells, which could influence response to treatment and clinical behavior of the disease.


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