Immunotherapeutics in the Management of Metastatic Melanoma Immunotherapeutics in the Management of Metastatic Melanoma
Advances in immunotherapeutics in the last decade have drastically changed the outlook for patients with metastatic melanoma. Review the currently available immunotherapies in this update.Skin Therapy Letter
Condition: Uveal Melanoma Interventions: Drug: ADI PEG20; Drug: Nivolumab; Drug: Ipilimumab Sponsor: Memorial Sloan Kettering Cancer Center Recruiting
We recently reported that serum levels of interleukin (IL)-6 were increased in melanoma patients who developed neutrophil-rich psoriasiform dermatitis during immunotherapies with anti-programmed cell death 1 (PD-1) antibodies. To identify the roles of IL-6 in its pathogenesis, a murine model of imiquimod (IMQ)-induced psoriasiform dermatitis was used, by which we analyzed the difference between PD-1 deficient (PD-1-/-) mice and wild-type (WT) mice. PD-1-/- mice presented significantly more severe psoriasiform dermatitis with thicker ear swelling and higher PASI score, representing the severities of erythema, scaling and sk...
Successful immunotherapy strategies for melanoma must elicit the infiltration of CD8+ T cells into the tumor, which is mediated by the recognition of tumor-derived, cytosolic DNA by the cGAS –STING-type I interferon (IFN) signaling pathway in tumor-infiltrating dendritic cells. However, cytosolic DNA can also be recognized by AIM2, a cytosolic DNA sensor that generates IL-1β and IL-18, and also induces pyroptosis, whose function in the melanoma microenvironment remains unclear. Here we report that an intravenously injected premelanosome protein (PMEL) peptide-pulsed Aim2-deficient dendritic cell vaccine (Aim2&mi...
Melanoma is the leading cause of skin cancer death in the United States, with a 5-year survival rate of 20% for patients with advanced disease. The development of targeted therapies and immunotherapy has helped improve survival for some patients, but many others still face significant therapeutic challenges, including resistance to therapy and relapse of their disease. Furthermore, our understanding of the steps involved in melanoma initiation and progression is incomplete. We are interested in uncovering factors involved in melanoma initiation and progression with a focus on identifying those key factors that have therapeutic potential.
Cancer persister cells survive cytotoxic therapies by entering a drug-tolerant, pro-survival cell state governed by poorly understood nongenetic mechanisms. Persister cells have been observed in a wide range of tumor types and are known to exhibit tolerance to targeted therapies and chemotherapies. Key characteristics of persister cells include reversible drug-tolerance, quiescence/slow proliferation, low genome-wide H3K4me3 marks, cancer stem cell and EMT gene expression patterns, and cross resistance to other cytotoxic drugs.
Background: Both surgical treatment and targeting or immunotherapy of melanoma are based on the heterogeneity of melanoma. The lack of studies on primary acral subtype melanoma is mainly due to technical limitations of sample acquiring and sequencing. Objective: To study the heterogeneity of CNV in primary acral subtype melanoma at a variety of levels. Methods: Using LCM and MALBAC (Multiple Annealing and Looping Based Amplification Cycles) to portray the landscape of CNVs in 7 cases of primary acral subtype melanoma.
Conventional monotherapies only benefit a minority of melanoma patients while combined immunotherapy exhibited extremely high rates of treatment-related adverse events. Herein, we created a multifunctional and immunogenic nanoplatform, AuNR@mSiO2@DOX-CuxS-PEG, which integrating photothermal properties of gold nanoparticles, photodynamic properties of CuxS and chemotherapy into a single nanoplatform. Upon near-infrared laser irradiation (NIR), the CuxS were uncapped and triggered chemotherapy drugs release into tumor environment.
Tumor infiltrated lymphocyte (TIL) into the melanoma microenvironment has been associated with improved survival for some patients and also has been exploited to grow TIL in vitro for adoptive therapy. However, prognostic significance of immune infiltrating cells in melanoma and other tumors remains a relatively new concept, and markers related to suppressive versus active functional TIL remain unclear. From an ongoing clinical trial using TIL intended for adoptive immunotherapy, we have studied the melanoma patient tumors specimens (FFPE) from 20 patients whose autologous TIL lines grew to sufficient number for possible use clinically.
Analogous to epigenetic regulation of gene expression through the reversible DNA and histone modifications, post-transcriptional N6-methyladenosine (m6A) methylation of adenosine residues in mRNA as well as lncRNA provides an additional layer of regulation that may alter mRNA metabolism and gene expression. Recently, m6A RNA methylation research was revived by the discovery of the fat mass- and obesity-associated protein (FTO) as the first RNA demethylase, implying that m6A RNA methylation is a reversible and dynamic modification and may have critical biological functions.
Nivolumab is a programmed cell death (PD)-1 ligand inhibitor used in treatment of melanoma and other malignancies. Immune-related adverse events (IRAEs) affect nearly all organ systems, most commonly the skin, the gastrointestinal tract (enterocolitis), the liver (hepatitis), and the endocrine system. Skin reactions related to immunotherapy occur in 4-27% of patients, including lichenoid mucocutaneous eruptions, vitiligo, psoriasis, lichen planus, and bullous pemphigoid. Most recently, genital lichen sclerosus (LS) and relapse of morphea have been reported.