The prognostic landscape of adaptive immune resistance signatures and infiltrating immune cells in the tumor microenvironment of uveal melanoma.

This study analyzed the immune landscape of adaptive immune resistance signatures and infiltrating immune cells in the TME of UM. Identification of these immune-related biomarkers may thus enable the prediction of prognosis and the selection of optimal immunotherapy strategies in UM. PMID: 32439398 [PubMed - as supplied by publisher]
Source: Experimental Eye Research - Category: Opthalmology Authors: Tags: Exp Eye Res Source Type: research

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Malignant melanoma is the most deadly form of skin cancer. It originates from melanocytic cells and can also arise at other body sites. Early diagnosis and appropriate medical care offer excellent prognosis with up to 5-year survival rate in more than 95% of all patients. However, long-term survival rate for metastatic melanoma patients remains at only 5%. Indeed, malignant melanoma is known for its notorious resistance to most current therapies and is characterized by both genetic and epigenetic alterations. In cutaneous melanoma (CM), genetic alterations have been implicated in drug resistance, yet the main cause of this...
Source: Theranostics - Category: Molecular Biology Authors: Tags: Review Source Type: research
Conclusions: The infiltration of immune cells in 32 cancer types was quantified, and considerable heterogeneity was observed in the prognostic relevance of these cells in different cancer types. An ICCS model was constructed for LUAD with competent prognostic performance, which can further deepen our understanding of the TME of LUAD and can have implications for immunotherapy.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
n Utikal Tumorigenesis is correlated with abnormal expression and activity of G protein-coupled receptors (GPCRs) and associated G proteins. Oncogenic mutations in both GPCRs and G proteins (GNAS, GNAQ or GNA11) encoding genes have been identified in a significant number of tumors. Interestingly, uveal melanoma driver mutations in GNAQ/GNA11 were identified for a decade, but their discovery did not lead to mutation-specific drug development, unlike it the case for BRAF mutations in cutaneous melanoma which saw enormous success. Moreover, new immunotherapies strategies such as immune checkpoint inhibitors have given und...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Abstract Immunotherapy has recently become a powerful weapon against cancer. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) was the first immune checkpoint used for immunotherapy. However, CTLA-4-related mechanisms in various cancers have not been comprehensively investigated. This aim of this study was an in-depth investigation of CTLA-4 in the tumor microenvironment and its relationship with other immunomodulators, immune-related pathways and survival outcomes of 33 cancer types. Overall 9,743 tumor samples and 710 normal samples of 33 cancer types from The Cancer Genome Atlas (TCGA) database were included...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
(University of Turku) New study from researchers in Finland and the United Kingdom reveals that tumors lacking a protein called BAP1 have an ineffective immune reaction against cancer, thus rendering immunotherapies ineffectual, particularly in uveal melanomas (UM). The researchers also discovered that when BAP1 is lost, other molecules will be present in order to support cancer growth. Luckily, some of these molecules can be targeted with existing drugs, which can lead to the development of novel immunotherapies.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
CONCLUSIONS: Our findings suggest that GNAQ/11 mutant non-uveal melanomas are a melanoma subtype distinct both clinically and genetically from cutaneous and uveal melanoma. As they respond poorly to available treatment regimens, novel effective therapeutic approaches for affected patients are urgently needed. PMID: 32064597 [PubMed - as supplied by publisher]
Source: The British Journal of Dermatology - Category: Dermatology Authors: Tags: Br J Dermatol Source Type: research
Orloff Sato Uveal melanoma (UM) is the most common primary eye malignancy in adults and up to 50% of patients subsequently develop systemic metastasis. Metastatic uveal melanoma (MUM) is highly resistant to immunotherapy. One of the mechanisms for resistance would be the immune-suppressive tumor microenvironment. Here, we have investigated the role of tryptophan 2,3-dioxygenase (TDO) in UM. Both TDO and indoleamine 2,3-dioxygenase (IDO) catalyze tryptophan and produce kynurenine, which could cause inhibition of T cell immune responses. We first studied the expression of TDO on tumor tissue specimens obtained fro...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
In this study, we used bioinformatic methods to investigate the immune infiltration of uveal melanoma samples in public datasets. We first performed Gene Set Enrichment/Variation Analyses to detect immunological pathways that are altered in tumors with monosomy 3 or BAP1 deficiency. We then conducted an unsupervised clustering analysis to identify distinct immunologic molecular subtypes of uveal melanoma. We used CIBERSORT and ESTIMATE with RNA-seq data from The Cancer Genome Atlas and the GSE22138 microarray dataset to determine the sample-level immune subpopulations and immune scores of uveal melanoma samples. The Kaplan...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
Authors: Martel A, Hamedani M, Lagier J, Bertolotto C, Gastaud L, Poissonnet G Abstract INTRODUCTION: Orbital exenteration is a radical anatomically and psychologically disfiguring procedure. It is mostly performed for management of orbital cancers or cancers with orbital involvement. The lack of benefit in terms of overall survival and the development of new molecular therapies (targeted therapies, immunotherapy) in recent years leads us to question its use. The goal of our review is to answer to the following question: is orbital exenteration a viable procedure in 2019? MATERIALS AND METHODS: A literature rev...
Source: Journal Francais d Ophtalmologie - Category: Opthalmology Tags: J Fr Ophtalmol Source Type: research
ConclusionsThe tolerability of the combined checkpoint blockade in UM may possibly be better than in trials on cutaneous melanoma. This study implies that combined checkpoint blockade represents the hitherto most effective treatment option available for metastatic UM available outside of clinical trials.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
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