Extracellular adenosine metabolism in immune cells in melanoma

Abstract Malignant melanoma is characterized by the development of chronic inflammation in the tumor microenvironment, which leads to a strong immunosuppression associated with a rapid tumor progression. Adenosine is considered as one of the main immunosuppressive factors in the tumor environment. It is produced via enzymatic hydrolysis of extracellular ATP by ectonucleotidases CD39 and CD73 localized on cell surface. Using the ret transgenic mouse melanoma model that closely mimics human melanoma, we demonstrated an increased frequency of ectonucleotidase-positive myeloid-derived suppressor cells (MDSCs) in melanoma lesions and lymphoid organs. Furthermore, we observed that conventional CD4+FoxP3− and CD8+ T cells infiltrating melanoma lesions of ret transgenic mice were distinctly enriched in the CD39+CD73+ subpopulation that co-expressed also PD-1. Ectonucleotidase expression was also up-regulated in CD4+ and CD8+ T cells upon activation. In addition, these ectoenzymes were largely found to be expressed on memory T cell compartment (in particular, on effector memory cells). Our data suggest that extracellular adenosine produced by regulatory T cells (Tregs) and MDSCs can suppress T cell effector functions through paracrine signaling. Another mechanism involves its production also by effector T cells and an inhibition of their anti-tumor reactivity via autocrine signaling as a part of the negative feedback loop. This mode of adenosine signaling could be also...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Publication date: Available online 17 August 2019Source: Seminars in Cancer BiologyAuthor(s): Paola Queirolo, Andrea Boutros, Enrica Tanda, Francesco Spagnolo, Pietro QuaglinoAbstractMelanoma has always been described as an immunogenic tumor. Despite that, until 2011 the standard of care in metastatic melanoma was chemotherapy, with low response rates and no clear impact on overall survival. Melanoma was the first cancer type to drive the use of immune-checkpoint inhibitors into clinical practice, which revolutionized the therapeutic paradigm not only in melanoma, but also in an increasing number of tumors. In this review,...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
We appreciate the interest that Roncati and Piscioli showed in our recent publication, in which we evaluated the risk of sentinel lymph node (SLN) metastases in nonulcerated, T1b melanoma by the new 8th edition American Joint Committee on Cancer (AJCC) staging criteria.1 The authors propose a model of melanoma progression based on the transition from a radial growth phase to a vertical growth phase (VGP) that can predict biologic aggressiveness and propensity to metastasize.
Source: Journal of the American College of Surgeons - Category: Surgery Authors: Tags: Letter Source Type: research
In comparison with the 7th Edition, the 8th Edition of the American Joint Committee on Cancer (AJCC) staging system for melanoma no longer considers the mitotic count in the a or b T1 categorization, but it adopts a sub-stratification based on Breslow depth: T1a ≤ 0.8 mm without ulceration and T1b ≤ 0.8 mm with ulceration or 0.8 to 1 mm with or without ulceration. Skin melanoma can be subdivided by Breslow depth into thin melanoma (≤1 mm) or thick melanoma (>1  mm). According to the AJCC 8th Edition, a and b specifications are assigned based on ulceration and depth, which replace the mitotic count for square millimeter.
Source: Journal of the American College of Surgeons - Category: Surgery Authors: Tags: Letter Source Type: research
este Lebbe Samia Mourah In BRAFV600mut metastatic melanoma, the combination of BRAF and MEK inhibitors (BRAFi, MEKi) has undergone multiple resistance mechanisms, limiting its clinical benefit and resulting in the need for response predicting biomarkers. Based on phase III clinical trial data, several studies have previously explored baseline genomic features associated with response to BRAFi + MEKi. Using a targeted approach that combines the examination of mRNA expression and DNA alterations in a subset of genes, we performed an analysis of baseline genomic alterations involved in MAPK inhibitors’ resista...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
P. M. Luyten Martine J. Jager A high HLA expression in uveal melanoma (UM) is part of the prognostically unfavorable inflammatory phenotype. We wondered whether the presence of soluble HLA (sHLA) in the aqueous humour is associated with clinical, histopathological or genetic tumour characteristics, and represents tumour HLA expression and intratumoural inflammation. Aqueous humour from 108 UM patients was analysed for the presence of sHLA, using a Luminex assay specific for HLA Class I. Clinical and genetic parameters were compared between sHLA-positive and negative eyes. A qPCR analysis was performed on tumour tiss...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Conclusions: Whereas in myelodysplastic syndrome predominantly missense SRSF2 mutations are described, the observed SRSF2 mutations in UM are all in-frame deletions of 8–9 amino acids. This suggests that the R625 missense SF3B1 mutations and SRSF2 mutations in UM are different compared to the spliceosome gene mutations in hematological cancers, and probably target a different, as yet unknown, set of genes involved in uveal melanoma etiology.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Communication Source Type: research
We describe a case series of nine patients with metastatic melanoma and injectable lesions who developed progressive disease under a PD-1 inhibitor monotherapy. At the time of progressive disease, patients received intratumoral IL-2 treatment in addition to PD-1 inhibitor therapy. Three patients showed complete, three patients partial response and three patients progressive disease upon this combination therapy. IHC stainings were performed from metastases available at baseline (start of PD-1 inhibitor) and under combination therapy with IL-2. IHC results revealed a significant increase of CD4+ and CD8+ T cells and a highe...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Authors: Hao J, Li S, Li J, Jiang Z, Ghaffar M, Wang M, Jia R, Chen S, Wang Y, Zeng Y Abstract Esophageal carcinoma (EC) is the sixth most deadly of all cancers. It is among the most malignant cancers due to its highly aggressive nature and low survival rate. The incidence of EC is high in Asia, particularly in Southern areas including China, Iran and Japan. There is a large body of evidence to suggest an association between the melanoma antigen gene (MAGE) family and the initiation of cancer; however, there is no clear evidence to suggest an association between EC and MAGE. Discovery of the chemical and physiologi...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
rner Niels Schaft Chimeric antigen receptor (CAR)-T cells already showed impressive clinical regressions in leukemia and lymphoma. However, the development of CAR-T cells against solid tumors lags behind. Here we present the clinical-scale production of CAR-T cells for the treatment of melanoma under full GMP compliance. In this approach a CAR, specific for chondroitin sulfate proteoglycan 4 (CSPG4) is intentionally transiently expressed by mRNA electroporation for safety reasons. The clinical-scale protocol was optimized for: (i) expansion of T cells, (ii) electroporation efficiency, (iii) viability, (iv) cryopreser...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Technical Note Source Type: research
In this study we further explored the associations of these with melanoma, in addition to deprivation and socio-economic stressors. In this analysis of 2183 population-ascertained primary cutaneous melanoma patients; clinical, demographic and socio-economic variables were assessed as predictors of tumour thickness, melanoma death and overall death.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Original Article Source Type: research
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