Medical bioinformatics in melanoma

Purpose of review Bioinformatic insights from next-generation sequencing has been integral in understanding melanoma biology, resistance to treatment and provided new avenues for melanoma treatment. Whole-genome sequencing, whole-exome sequencing and RNA sequencing has redefined the molecular classification of melanoma, revealed distinct genetic aberrations that define clinical subtypes of melanoma and uncovered the diverse heterogeneity that resides in an individual tumor. Recent findings In this review, we will summarize the recent whole-genome study that catalogs the genomic landscape across many melanoma subtypes, the single-cell RNA sequencing studies that interrogates tumor heterogeneity and the personalized vaccine approaches to melanoma treatment. Summary Whole-genome sequencing of diverse subtypes of melanoma revealed acral and mucosal subtypes to have a different genomic landscape compared with cutaneous melanoma. Acral and mucosal melanomas are characterized by low mutation burden and high structural variants. Single-cell RNA sequencing revealed high intratumoral heterogeneity and the existence of rare intrinsic drug-resistant populations. Lastly, vaccination against tumor neoantigens could be a potential personalized medicine therapy for melanoma patients. In summary, bioinformatics research is deeply ingrained in all aspects of melanoma research and will continue to blossom together for many years to come.
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: MELANOMA AND OTHER SKIN NEOPLASMS: Edited by Reinhard Dummer Source Type: research

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Adoptive cell therapy (ACT) consisting of genetically engineered T cells expressing tumor antigen-specific T-cell receptors displays robust initial antitumor activity, followed by loss of T-cell activity/persistence and frequent disease relapse. We characterized baseline and longitudinal T-cell phenotype variations resulting from different manufacturing and administration protocols in patients who received ACT. Patients with melanoma who enrolled in the F5-MART-1 clinical trial (NCT00910650) received infusions of MART-1 T-cell receptors transgenic T cells with MART-1 peptide-pulsed dendritic cell vaccination. Patients were...
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
AbstractBackgroundCancer-testis antigen NY-ESO-1 is a highly immunogenic melanoma antigen which has been incorporated into adjuvant vaccine clinical trials. Three such early-phase trials were conducted at our center among patients with high-risk resected melanoma. We herein report on the pooled long-term survival outcomes of these patients in comparison to historical controls.MethodsAll melanoma patients treated at NYU Langone Health under any of three prospective adjuvant NY-ESO-1 vaccine trials were retrospectively pooled into a single cohort. All such patients with stage III melanoma were subsequently compared to histor...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Oncologists in Spain are recruiting patients for the randomized phase of the pleural mesothelioma clinical trial involving ONCOS-102, the promising immunotherapy vaccine. Optimism surrounding the trial stems from encouraging results obtained recently in the six-patient safety cohort used as a precautionary lead-in. The trial involves the vaccine in combination with standard-of-care chemotherapy for patients with inoperable disease. ONCOS-102 is a scientifically engineered adenovirus that is designed to activate a patient’s immune system to selectively target cancer cells. It is being developed by Targovax, a Scandina...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Authors: Tucci M, Mannavola F, Passarelli A, Stucci LS, Cives M, Silvestris F Abstract Exosomes (Exo) are small vesicles produced by melanoma cells and the accessory cells of the tumor microenvironment. They emerge via both classical and direct pathways and actively participate in tumor colonisation of distant tissues. The proteins, nucleic acids, cytokines and growth factors engulfed by Exo are transferred to recipient cells, where they drive numerous functions required for the tumor escape from immune system control and tumor progression. By positively or negatively modulating immune cell properties, Exo provoke ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Authors: González FE, Chernobrovkin A, Pereda C, García-Salum T, Tittarelli A, López MN, Salazar-Onfray F, Zubarev RA Abstract Autologous dendritic cells (DCs) loaded with cancer cell-derived lysates have become a promising tool in cancer immunotherapy. During the last decade, we demonstrated that vaccination of advanced melanoma patients with autologous tumor antigen presenting cells (TAPCells) loaded with an allogeneic heat shock- (HS-) conditioned melanoma cell-derived lysate (called TRIMEL) is able to induce an antitumor immune response associated with a prolonged patient survival. TRIMEL p...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
Gas‑filled ultrasound microbubbles enhance the immunoactivity of the HSP70‑MAGEA1 fusion protein against MAGEA1‑expressing tumours. Mol Med Rep. 2018 May 09;: Authors: Gao X, Nan Y, Yuan Y, Gong X, Sun Y, Zhou H, Zong Y, Zhang L, Yu M Abstract Advanced malignant melanoma is characterized by rapid development, poor prognosis and insensitivity to chemoradiotherapy. Immunotherapy has become one of the primary clinical treatments for malignant melanomas. In recent decades, identifying specific tumour antigens and the enhanced immunoactivity of tumour vaccines has become critical for engineering succe...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
Abstract Cancer immunotherapy has shown tremendous progresses in recent years for various cancers and layered double hydroxide (LDH) nanoparticles are demonstrated as effective adjuvants for protein-based vaccines. This research further shows that the colloidal stability of LDH-based vaccines significantly influences the therapeutic efficacy and LDH nanoparticles are able to adjuvant multiple tumor-associated antigen peptides to provoke strong cell-mediated immune responses for effective inhibition of cancer growth. The LDH-based multi-target therapeutic vaccines were constructed by assembling epitope peptides and...
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research
Mariana Aris, Alicia In és Bravo, María Betina Pampena, Paula Alejandra Blanco, Ibel Carri, Daniel Koile, Patricio Yankilevich, Estrella Mariel Levy, María Marcela Barrio, José Mordoh
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Authors: Romano E, Rufo N, Korf H, Mathieu C, Garg AD, Agostinis P Abstract The hypoxia responsive protein BNIP3, plays an important role in promoting cell death and/or autophagy, ultimately resulting in a cancer type-dependent, tumour-enhancer or tumour-suppressor activity. We previously reported that in melanoma cells, BNIP3 regulates cellular morphology, mitochondrial clearance, cellular viability and maintains protein expression of CD47, a pro-cancerous, immunosuppressive 'don't eat me' signal. Surface exposed CD47 is often up-regulated by cancer cells to avoid clearance by phagocytes and to suppress immunogeni...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Tumor-derived, cytosolic DNA has been reported to stimulate the production of type I interferon (IFN) through a STING-dependent signaling pathway in dendritic cells (DCs), which helps to initiate a spontaneous T cell response against melanoma. However, cytosolic DNA can also be recognized by AIM2, a cytosolic innate immune sensor, whose function in melanoma remains unclear. To determine the role of AIM2 in melanoma microenvironment, we subcutaneously challenged Aim2/ mice with B16F10 melanoma. Surprisingly, these mice exhibited a lower tumor burden with fewer tumor-infiltrating regulatory T cells (Tregs) than WT mice, indi...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Pigmentation and Melanoma Source Type: research
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