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Melanoma immunotherapy

Mario Mandalà, Piotr Rutkowski
The recent advances in cancer immunotherapy with unprecedented success in therapy of advanced melanoma represent a turning point in the landscape of melanoma treatment. Given the complexity of activation of immunological system and the physiologic multifactorial homeostatic mechanisms controlling immune responses, combinatorial strategies are eagerly needed in melanoma therapy. Nevertheless, rational selection of immunotherapy combinations should be more biomarker-guided, including not only the cancer immunogram, PD-L1 expression, interferon gene expression signature, mutational burden, and tumor infiltration by CD8+ T cells but also intratumoral T cell exhaustion and microbiota composition...
December 14, 2018: Virchows Archiv: An International Journal of Pathology
Renata Ottes Vasconcelos, Simona Serini, Ana Paula de Souza Votto, Gilma Santos Trindade, Caterina Fanali, Alessandro Sgambato, Gabriella Calviello
The recently developed therapeutic strategies have led to unprecedented improvements in the control of metastatic melanoma and in the survival of specific subgroups of patients. However, drug resistance, low response rates, and undesired side effects make these treatments not suitable or tolerable for all the patients, and chemotherapeutic treatments appear still indispensable, at least for subgroups of patients. New combinatory strategies are also under investigation as tailored treatments or salvage therapies, including combined treatments of immunotherapy with conventional chemotherapy...
December 13, 2018: Melanoma Research
Lukas W Pfannenstiel, Corey McNeilly, Chaomei Xiang, Kai Kang, Claudia Marcella Diaz-Montero, Jennifer S Yu, Brian R Gastman
Nearly half of melanoma patients develop brain metastases during the course of their disease. Despite advances in both localized radiation and systemic immunotherapy, brain metastases remain difficult to treat, with most patients surviving less than 5 months from the time of diagnosis. While both treatment regimens have individually shown considerable promise in treating metastatic melanoma, there is interest in combining these strategies to take advantage of potential synergy. In order to study the ability of local radiation and anti-PD-1 immunotherapy to induce beneficial anti-tumor immune responses against distant, unirradiated tumors, we used two mouse models of metastatic melanoma in the brain, representing BRAF mutant and non-mutant tumors...
2019: Oncoimmunology
Hyung-Joon Kwon, Heejae Lee, Go-Eun Choi, Soon Jae Kwon, Ah Young Song, So Jeong Kim, Woo Seon Choi, Sang-Hyun Hwang, Sun Chang Kim, Hun Sik Kim
Ginsenosides are the principal active components of ginseng and are considered attractive candidates for combination cancer therapy because they can kill tumors and have favorable safety profiles. However, the overall benefit of ginsenosides remains unclear, particularly in cancer immunosurveillance, considering the controversial results showing repression or promotion of immune responses. Here we identify a potentiating role of ginsenoside F1 (G-F1) in cancer surveillance by natural killer (NK) cells. Among 15 different ginsenosides, G-F1 most potently enhanced NK cell cytotoxicity in response to diverse activating receptors and cancer cells...
2018: Frontiers in Immunology
Julia Brütting, Theresa Steeb, Lydia Reinhardt, Carola Berking, Friedegund Meier
BACKGROUND: Patients diagnosed with melanoma frequently search the internet for treatment information, including novel and complex immunotherapy. However, health literacy is limited among half of the German population, and no assessment of websites on melanoma treatment has been performed so far. OBJECTIVE: The aim of this study was to identify and assess the most visible websites in German language on melanoma immunotherapy. METHODS: In accordance with the common Web-based information-seeking behavior of patients with cancer, the first 20 hits on Google, Yahoo, and Bing were searched for combinations of German synonyms for "melanoma" and "immunotherapy" in July 2017...
December 13, 2018: JMIR Cancer
Guilan Shi, Chelsea Edelblute, Sezgi Arpag, Cathryn Lundberg, Richard Heller
Metastatic melanoma is an aggressive skin cancer with a relatively low survival rate. Immune-based therapies have shown promise in the treatment of melanoma, but overall complete response rates are still low. Previous studies have demonstrated the potential of plasmid IL-12 (pIL-12) delivered by gene electrotransfer (GET) to be an effective immunotherapy for melanoma. However, events occurring in the tumor microenvironment following delivery have not been delineated. Therefore, utilizing a B16F10 mouse melanoma model, we evaluated changes in the tumor microenvironment following delivery of pIL-12 using different GET parameters or injection of plasmid alone...
December 8, 2018: Cancers
Praveen K Bommareddy, Salvatore Aspromonte, Andrew Zloza, Samuel D Rabkin, Howard L Kaufman
Melanoma is an aggressive cutaneous malignancy, but advances over the past decade have resulted in multiple new therapeutic options, including molecularly targeted therapy, immunotherapy, and oncolytic virus therapy. Talimogene laherparepvec (T-VEC) is a herpes simplex type 1 oncolytic virus, and trametinib is a MEK inhibitor approved for treatment of melanoma. Therapeutic responses with T-VEC are often limited, and BRAF/MEK inhibition is complicated by drug resistance. We observed that the combination of T-VEC and trametinib resulted in enhanced melanoma cell death in vitro...
December 12, 2018: Science Translational Medicine
Isabella C Glitza Oliva, Rana Alqusairi
While melanoma is less common than some other skin cancers, it is responsible for nearly 10,000 deaths in the USA each year alone. For many decades, very limited treatment options were available for patients with metastatic melanoma. However, recent breakthroughs have brought new hopes for patients and providers.While targeted therapy with BRAF and MEK inhibitors represents an important cornerstone in the treatment of metastatic melanoma, this chapter carefully reviews the past and current therapy options available, with a significant focus on immunotherapy-based approaches...
2018: Advances in Experimental Medicine and Biology
Alice Indini, Lorenza Di Guardo, Carolina Cimminiello, Michele Prisciandaro, Giovanni Randon, Filippo De Braud, Michele Del Vecchio
BACKGROUND: Therapeutic chances for metastatic melanoma have consistently changed over the last years with the advent of antibodies targeting the programmed cell death protein-1 (PD-1). Onset of immune-related adverse events (irAEs) during treatment can be a source of concern, and the association with survival outcome is yet to be defined. PATIENTS AND METHODS: Data of consecutive patients treated with anti-PD1 (nivolumab or pembrolizumab) for metastatic melanoma between July 2013 and January 2018 were retrospectively reviewed...
December 11, 2018: Journal of Cancer Research and Clinical Oncology
Sun-Hee Kim, Jason Roszik, Sung-Nam Cho, Dai Ogata, Denai R Milton, Weiyi Peng, David Menter, Suhendan Ekmekcioglu, Elizabeth A Grimm
PURPOSE: Microsomal prostaglandin E2 synthase 1 (mPGES1) was evaluated as an important downstream effector of the cyclooxygenase 2 (COX2) pathway responsible for tumor-mediated immunosuppression in melanoma. EXPERIMENTAL DESIGN: The analysis of a Stage III melanoma tissue microarray (n=91) was performed to assess the association between mPGES1, COX2, CD8, and patient survival. Pharmacological inhibitors and syngeneic mouse models using mPGES1 knockout mouse melanoma cell lines were used to evaluate the mPGES1-mediated immunosuppressive function...
December 11, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Peter Mohr, Sebastian Haferkamp, Andreas Pinter, Carsten Weishaupt, Margit A Huber, Gerald Downey, Katarina Öhrling, Carmen Loquai, Karly S Louie
INTRODUCTION: Talimogene laherparepvec is a first-in-class oncolytic immunotherapy for intratumoral injection with proven efficacy and tolerability in patients with unresectable early metastatic melanoma (stage IIIB-IVM1a) in the pivotal phase III OPTiM study. The objective was to characterize melanoma patients treated with talimogene laherparepvec in routine clinical practice in Germany. METHODS: A retrospective chart review was conducted in unresectable stage IIIB-IVM1a melanoma patients...
December 7, 2018: Advances in Therapy
Cecilia Orbegoso, Krithika Murali, Susana Banerjee
Immunotherapy has been proven effective in several tumours, hence diverse immune checkpoint inhibitors are currently licensed for the treatment of melanoma, kidney cancer, lung cancer and most recently, tumours with microsatellite instability. There is much enthusiasm for investigating this approach in gynaecological cancers and the possibility that immunotherapy might become part of the therapeutic landscape for gynaecological malignancies. Cervical cancer is the fourth most frequent cancer in women worldwide and represents 7...
November 2018: Reports of Practical Oncology and Radiotherapy
Hayley Leeman, Elwira Kaminska, Deborah Green, Mark Bodman-Smith, Andrew Gravett, Katherine Bodman-Smith, John Copier, Gary Coulton, Alberto Fusi, Angus G Dalgleish
BACKGROUND: Despite the majority of patients do not gain any benefit from dendritic cells (DC) vaccines, this approach has occasionally given rise to dramatic responses in melanoma. Biomarkers are crucial to identify which patients are more likely to respond. We looked for correlations between pre- or post- vaccination biomarkers and clinical outcomes to DC therapy in a cohort of patients with stage IV melanoma receiving a vaccine with autologous ex-vivo expanded DCs pulsed with allogeneic tumor cell lysate...
December 7, 2018: Translational Oncology
Nicolas Delanoy, Jean-Marie Michot, Thibault Comont, Nora Kramkimel, Julien Lazarovici, Romain Dupont, Stéphane Champiat, Claude Chahine, Caroline Robert, Charles Herbaux, Benjamin Besse, Aude Guillemin, Christine Mateus, Patricia Pautier, Philippe Saïag, Emanuela Madonna, Marie Maerevoet, Jean-Christophe Bout, Charlotte Leduc, Pascal Biscay, Gilles Quere, Charlée Nardin, Mikael Ebbo, Laurence Albigès, Grégoire Marret, Virginie Levrat, Cécile Dujon, Jacques Vargaftig, Salim Laghouati, Laure Croisille, Anne-Laure Voisin, Bertrand Godeau, Christophe Massard, Vincent Ribrag, Aurélien Marabelle, Marc Michel, Olivier Lambotte
BACKGROUND: Anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) antibodies are novel immunotherapies for cancer that can induce immune-related adverse events (irAEs). These adverse events can involve all organs, including the haemopoietic system. Thus far, haematological irAEs (haem-irAEs) have not been extensively characterised. This study aims to provide a comprehensive report of the haem-irAEs induced by anti-PD-1 or anti-PD-L1. METHODS: In this descriptive observational study, we included consecutive patients aged at least 18 years with grade 2 or worse haem-irAEs induced by anti-PD-1 or anti-PD-L1 immunotherapy registered in three French pharmacovigilance databases: the Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC; a prospective registry of patients treated with anti-PD-1 or anti-PD-L1 at a single centre), the ImmunoTOX committee of Gustave Roussy (a national referral database of suspected irAEs in patients treated with immunotherapy), and the registry of the Centre de Référence des Cytopénies Auto-Immunes de l'Adulte (CeReCAI; a national database of autoimmune cytopenias)...
December 4, 2018: Lancet Haematology
C Longvert, P Saiag
Incidence of malignant melanoma has been increasing since the 1980s. For loco-regional stages, surgery is still the best treatment. Melanoma has a high distant metastatic potential and prognosis of advanced stages was until recently very poor. Since 2011 however, a real revolution has taken place in the treatment of metastatic melanoma. This is based upon considerably improved knowledge of the molecular mechanisms of melanoma and cancer immunology. Thus, two new classes of systemic therapeutic agents are now available: immunotherapies (immunological checkpoint inhibitors), which increase the antitumor immune response, and targeted therapies (BRAF and MEK inhibitors) for patients with BRAF V600-mutant melanoma...
December 5, 2018: La Revue de Médecine Interne
Jan Budczies, Anja Seidel, Petros Christopoulos, Volker Endris, Matthias Kloor, Balázs Győrffy, Barbara Seliger, Peter Schirmacher, Albrecht Stenzinger, Carsten Denkert
Harnessing the immune system by checkpoint blockade has greatly expanded the therapeutic options for advanced cancer. Since the efficacy of immunotherapies is influenced by the molecular make-up of the tumor and its crosstalk with the immune system, comprehensive analysis of genetic and immunologic tumor characteristics is essential to gain insight into mechanisms of therapy response and resistance. We investigated the association of immune cell contexture and tumor genetics including tumor mutational burden (TMB), copy number alteration (CNA) load, mutant allele heterogeneity (MATH) and specific mutational signatures (MutSigs) using TCGA data of 5722 tumor samples from 21 cancer types...
2018: Oncoimmunology
Jonathan G Pol, Sarah Lévesque, Samuel T Workenhe, Shashi Gujar, Fabrice Le Boeuf, Derek R Clements, Jean-Eudes Fahrner, Laetitia Fend, John C Bell, Karen L Mossman, Jitka Fucikova, Radek Spisek, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Oncolytic viruses selectively target and kill cancer cells in an immunogenic fashion, thus supporting the establishment of therapeutically relevant tumor-specific immune responses. In 2015, the US Food and Drug Administration (FDA) approved the oncolytic herpes simplex virus T-VEC for use in advanced melanoma patients. Since then, a plethora of trials has been initiated to assess the safety and efficacy of multiple oncolytic viruses in patients affected with various malignancies. Here, we summarize recent preclinical and clinical progress in the field of oncolytic virotherapy...
2018: Oncoimmunology
Alexander Liede, Rohini K Hernandez, Sally W Wade, Ronghai Bo, Nathan C Nussbaum, Elizabeth Ahern, William C Dougall, Mark J Smyth
After a case report of profound clinical response in a melanoma patient following treatment with an immune checkpoint inhibitor (ICI) and RANK-ligand inhibitor denosumab, we identified similar patients from electronic health records (EHR) and described patient characteristics and outcomes. This 2017 observational study used Flatiron Health's EHR database from ~255 US cancer clinics. Included were advanced melanoma or non-small-cell lung cancer (NSCLC) patients who received denosumab within 30 days of CTLA-4 (ipilimumab) or PD1 (pembrolizumab, nivolumab) inhibitors start with a minimum of 6 months of follow up...
2018: Oncoimmunology
Belinda Palermo, Ornella Franzese, Cosmo Di Donna, Mariangela Panetta, Concetta Quintarelli, Isabella Sperduti, Novella Gualtieri, Maria Laura Foddai, Enrico Proietti, Virginia Ferraresi, Gennaro Ciliberto, Paola Nisticò
We have recently described that DNA-damage inducing drug DTIC, administered before peptide (Melan-A and gp100)-vaccination, improves anti-tumor CD8+ Melan-A-specific T-cell functionality, enlarges the Melan-A+ TCR repertoire and impacts the overall survival of melanoma patients. To identify whether the two Ags employed in the vaccination differently shape the anti-tumor response, herein we have carried out a detailed analysis of phenotype, anti-tumor functionality and TCR repertoire in treatment-driven gp100-specific CD8+ T cells, in the same patients previously analyzed for Melan-A...
2018: Oncoimmunology
Neda Yaghoubi, Arash Soltani, Kiarash Ghazvini, Seyed Mahdi Hassanian, Seyed Isaac Hashemy
Colorectal cancer (CRC), as a prominent cause of cancer-related deaths, has historically been notable worldwide and many attempts have been made to raise the overall survival of CRC patients. Immune response has long been a question of great interest in a wide range of fields such as cancer therapies and anti-tumor immunity through checkpoint inhibitors, specifically anti PD-1/ PD-L1 interaction, is a new line of research for treatment of CRC patients. Following the successful development of anti-PD-1 for melanoma, renal cell carcinoma, and non-small cell lung cancer, several clinical trials have been conducted on monoclonal antibodies (MAbs) against PD-1 in CRC...
December 3, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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