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Melanoma immunotherapy

Malina Xiao, Muhammad Zaeem Noman, Ludovic Menard, Andy Chevigne, Martyna Szpakowska, Manon Bosseler, Markus Ollert, Guy Berchem, Bassam Janji
Autophagy is a quality control process executed at the basal level in almost all cell types. However, in cancer cells, autophagy is activated by several stimuli, including hypoxia. Depending on tumor type, stage, and genetic context, autophagy is a double-edged sword. Autophagy promotes regression in newly established tumors; however, it supports tumor progression in well-established tumors by maintaining cancer cell survival under stress conditions. These data, in addition to the emerging role of autophagy in impairing antitumor immunity, have attracted significant interest in developing autophagy inhibitors as a new approach to cancer treatment...
2018: Critical Reviews in Oncogenesis
Xiao Song, Chengli Guo, Yutian Zheng, Ying Wang, Zhongtian Jin, Yanhui Yin
BACKGROUND: Cancer/testis antigen MAGEC2 (also known as HCA587) is highly expressed in a wide variety of tumors and plays an active role in promoting growth and metastasis of tumor cells. However, little is known for the regulation of MAGEC2 expression in cancer cells. METHODS: Western blotting and quantitative RT-PCR were performed to analyze MAGEC2 expression. Co-immunoprecipitation assay was applied for detecting the endogenous interaction of MAGEC2 and TRIM28 in tumor cells...
October 11, 2018: BMC Cancer
Fausto Petrelli, Raffaele Ardito, Barbara Merelli, Veronica Lonati, Mary Cabiddu, Silvia Seghezzi, Sandro Barni, Antonio Ghidini
Levels of serum lactate dehydrogenase (LDH) are a recognized prognostic factor in malignant melanoma (MM). It is relevant to confirm its prognostic role in patients treated with targeted therapies [BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi)] and immunotherapy (IT). Furthermore, its role as a predictive marker in patients treated with these drugs had still not been investigated. We performed an electronic search for studies reporting information on overall survival (OS) or progression-free survival (PFS) according to LDH levels and on their predictive effect in patients treated with targeted therapies (BRAFi and MEKi) and IT...
October 10, 2018: Melanoma Research
Julie Garon-Czmil, Nadine Petitpain, Franck Rouby, Marion Sassier, Samy Babai, Mélissa Yelehe-Okouma, Georges Weryha, Marc Klein, Pierre Gillet
Immunotherapy with immune checkpoint inhibitors (ICIs) for cancer has become increasingly prescribed in recent years. Indeed, it is used to treat both solid and hematological malignancies due to their considerable potential in treating melanoma, non-small cell lung and other cancers. Immune-mediated related adverse endocrine toxicity, and especially thyroiditis, are seen as a growing problem needing specific screening and management. This study aims at describing thyroid dysfunctions induced by the ICIs marketed in France, which are registered in the French Pharmacovigilance database...
October 11, 2018: Fundamental & Clinical Pharmacology
Mengxue Dong, Zhefeng Meng, Kudelaidi Kuerban, Feilong Qi, Jiayang Liu, Yuxi Wei, Qian Wang, Shanshan Jiang, Meiqing Feng, Li Ye
Diosgenin, a natural steroidal saponin, can exert antitumor effect by regulating immune function and improving intestinal microbiota. The response to anti-PD-1 immunotherapy is associated with intestinal microbiota and effector T cells in tumor microenvironment. We hypothesize that the modulation of diosgenin on intestinal microbiota can facilitate antitumor immunity and the therapeutic efficacy of PD-1 antibody. In melanoma-bearing C57BL/6 mice, we observed that the anti-melanoma effect of diosgenin relied more on antitumor immunity than direct tumor inhibition activity evidenced by obvious CD4+ /CD8+ T-cell infiltration and IFN-γ expression in tumor tissues, and it could improve the compositions of intestinal microbiota...
October 10, 2018: Cell Death & Disease
Kendall F Moseley, Jarushka Naidoo, Clifton O Bingham, Michael A Carducci, Patrick M Forde, Geoffrey T Gibney, Evan J Lipson, Ami A Shah, William H Sharfman, Laura C Cappelli
BACKGROUND: The use of immune checkpoint inhibitors is increasing in cancer therapy today. It is critical that treatment teams become familiar with the organ systems potentially impacted by immune-related adverse events associated with these drugs. Here, we report adverse skeletal effects of immunotherapy, a phenomenon not previously described. CASE PRESENTATIONS: In this retrospective case series, clinical, laboratory and imaging data were obtained in patients referred to endocrinology or rheumatology with new fractures (n = 3) or resorptive bone lesions (n = 3) that developed while on agents targeting PD-1, CTLA-4 or both...
October 11, 2018: Journal for Immunotherapy of Cancer
Joanna Katarzyna Bujak, Rafał Pingwara, Michelle Hase Nelson, Kinga Majchrzak
Cancer immunotherapy is recently considered the most promising treatment for human patients with advanced tumors and could be effectively combined with conventional therapies such as chemotherapy or radiotherapy. Patients with hematological malignancies and melanoma have benefited greatly from immunotherapies such as, adoptive cell transfer therapy, experiencing durable remissions and prolonged survival. In the face of increasing enthusiasm for immunotherapy, particularly for the administration of tumor-specific T lymphocytes, the question arises whether this method could be employed to improve treatment outcomes for canine patients...
October 11, 2018: Acta Veterinaria Scandinavica
Fabian Finkelmeier, Oliver Waidmann, Joerg Trojan
T-cell checkpoint inhibition as a cancer treatment approach has been the main breakthrough in cancer treatment during the last years. Since the approval of the first commercial CTLA-4 antibody ipilimumab in 2011 for the treatment of melanoma, research and drug development in this field has accelerated massively. In 2014 the US Food and Drug Administration (FDA) approved the first PD-1 targeting agent, namely pembrolizumab, shortly followed by nivolumab. Areas covered: Nivolumab is a fully human immunoglobulin G4 anti-PD-1 monoclonal antibody which is approved for multiple advanced malignancies, including melanoma, non-small cell lung cancer, renal cell cancer, Hodgkin's lymphoma, squamous head and neck cancer and urothelial carcinoma...
October 10, 2018: Expert Review of Anticancer Therapy
W Loidl, F Luger
Urothelial carcinoma of the bladder is difficult to treat in advanced and metastatic stages. Several factors play a role: age, multimorbidity including impaired renal function and neuropathy make access to life-prolonging chemotherapy impossible in many cases. Improvements of response rates and overall survival in the second-line setting are not much different compared to best supportive care. However, the therapeutic landscape has changed dramatically during the last 2 years. Immunotherapies represented by checkpoint inhibitors have showed positive trial outcomes and have been approved by EMA (European Medicines Agency)...
October 9, 2018: Der Urologe. Ausg. A
T Hanley, S Papa, M Saha
Immunotherapy is now being routinely used in the management of many cancers. It is therefore vital that all clinicians are aware of the diverse array of cutaneous manifestations that can result from their use, which can vary from mild to life threatening.
October 2018: JRSM Open
Nina Dabrosin, Karen Sloth Juul, Jeanette Bæhr Georgsen, Simon Andrup, Henrik Schmidt, Torben Steiniche, Trine Heide Øllegaard, Louise Bønnelykke Behrndtz
Little is known about the infiltrative pattern of innate immune cells in primary melanoma compared with their paired metastases and in BRAF-mutated tumors. Therefore, our aim was to characterize the inflammatory microenvironment in primary ulcerated and nonulcerated melanomas and paired metastases, to investigate the relation between inflammation and BRAF mutation in primary melanoma and paired metastases, and to evaluate the effect of the analyzed biomarkers on melanoma-specific survival. A total of 385 primary tumors and 96 paired metastases were stained with immunohistochemistry for BRAF, CD163+ macrophages, CD123+ plasmacytoid dendritic cells, CD66b+ neutrophils, and E-cadherin and estimated using objective computer-assisted image analysis...
October 5, 2018: Melanoma Research
Amanda Rosewell Shaw, Masataka Suzuki
Adoptive T-cell immunotherapies, including chimeric antigen receptor-modified T-cells (CAR-T cells), have revolutionized cancer treatment, especially for hematologic malignancies. Clinical success of CAR-T cell monotherapy in solid tumors however, has been only modest. Oncolytic viruses provide direct cancer cell lysis, stimulate systemic immune responses, and have the capacity to provide therapeutic transgenes. Oncolytic virotherapy has shown great promise in many preclinical solid tumor models and the first oncolytic virus has been approved by the FDA for the treatment of advanced melanoma...
2018: Frontiers in Immunology
Chia-Jui Chang, Shih-Jen Chen, De-Kuang Hwang, Catherine Jui-Ling Liu
Immune checkpoint blockade therapy is relatively a new treatment for cancer which has shown promising results. However, immune-related side effects including uveitis have occasionally been reported during this therapy. Herein, we report the case of a 65-year-old male who suffered bilateral anterior uveitis after immune checkpoint blockade therapy with pembrolizumab and ipilimumab for malignant melanoma. His symptoms and signs improved after topical treatment with corticosteroids. Clinicians should be aware that uveitis can be an immune-related adverse event of immunotherapy...
July 2018: Taiwan Journal of Ophthalmology
G F Yin, W Guo, X H Chen, Z Y Liu, Z G Huang
Objective: To study the clinical characteristics of mucosal melanoma in the head and neck, including the risk factors affecting distant metastasis, recurrence and survival rate, and to provide the basis for the individualized treatment of mucosal melanoma in the head and neck. Methods: The clinical data of 117 cases of mucosal melanoma in the head and neck treated from January 2004 to June 2016 in Beijing Tongren Hospital were analyzed retrospectively, and the risk factors affecting the prognosis, distant metastasis and local recurrence were analyzed...
September 7, 2018: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
Hildur Helgadottir, Paola Ghiorzo, Remco van Doorn, Susana Puig, Max Levin, Richard Kefford, Martin Lauss, Paola Queirolo, Lorenza Pastorino, Ellen Kapiteijn, Miriam Potrony, Cristina Carrera, Håkan Olsson, Veronica Höiom, Göran Jönsson
BACKGROUND: Inherited CDKN2A mutation is a strong risk factor for cutaneous melanoma. Moreover, carriers have been found to have poor melanoma-specific survival. In this study, responses to novel immunotherapy agents in CDKN2A mutation carriers with metastatic melanoma were evaluated. METHODS: CDKN2A mutation carriers that have developed metastatic melanoma and undergone immunotherapy treatments were identified among carriers enrolled in follow-up studies for familial melanoma...
October 5, 2018: Journal of Medical Genetics
Bianca Simon, Ugur Uslu
Chimeric antigen receptor (CAR)-T cells are one of the impressive recent success stories of anti-cancer immunotherapy. Especially in hematological malignancies this treatment strategy has shown promising results leading to the recent approval of two CAR-T cell constructs targeting CD19 in the United States and the European Union. After the huge success in hematological cancers, the next step will be the evaluation of its efficacy in different solid tumors, which is currently investigated in preclinical as well as clinical settings...
October 4, 2018: Experimental Dermatology
Vanessa S Fear, Caitlin Tilsed, Jonathan Chee, Catherine A Forbes, Thomas Casey, Jessica N Solin, Sally M Lansley, W Joost Lesterhuis, Ian M Dick, Anna K Nowak, Bruce W Robinson, Richard A Lake, Scott A Fisher
Mesothelioma is an aggressive asbestos induced cancer with extremely poor prognosis and limited treatment options. Immune checkpoint blockade (ICPB) has demonstrated effective therapy in melanoma and is now being applied to other cancers, including mesothelioma. However, the efficacy of ICPB and which immune checkpoint combinations constitute the best therapeutic option for mesothelioma have yet to be fully elucidated. Here, we used our well characterised mesothelioma tumour model to investigate the efficacy of different ICBP treatments to generate effective therapy for mesothelioma...
2018: Oncoimmunology
Lillian Sun, Ellen Moore, Rose Berman, Paul E Clavijo, Anthony Saleh, Zhong Chen, Carter Van Waes, John Davies, Jay Friedman, Clint T Allen
Intrinsic resistance to cytotoxic T-lymphocyte (CTL) killing limits responses to immune activating anti-cancer therapies. Here, we established that activation of the G2/M cell cycle checkpoint results in tumor cell cycle pause and protection from granzyme B-induced cell death. This was reversed with WEE1 kinase inhibition, leading to enhanced CTL killing of antigen-positive tumor cells. Similarly, but at a later time point, cell cycle pause following TNFα exposure was reversed with WEE1 kinase inhibition, leading to CTL transmembrane TNFα-dependent induction of apoptosis and necroptosis in bystander antigen-negative tumor cells...
2018: Oncoimmunology
David L Bajor, Rosemarie Mick, Matthew J Riese, Alex C Huang, Brendan Sullivan, Lee P Richman, Drew A Torigian, Sangeeth M George, Erietta Stelekati, Fang Chen, J Joseph Melenhorst, Simon F Lacey, Xiaowei Xu, E John Wherry, Tara C Gangadhar, Ravi K Amaravadi, Lynn M Schuchter, Robert H Vonderheide
We report long-term clinical outcomes and immune responses observed from a phase 1 trial of agonist CD40 monoclonal antibody (mAb) and blocking CTLA-4 mAb in patients with metastatic melanoma. Twenty-four patients previously untreated with checkpoint blockade were enrolled. The agonistic CD40 mAb CP-870,893 and the CTLA-4 blocking mAb tremelimumab were dosed concomitantly every 3 weeks and 12 weeks, respectively, across four dose combinations. Two patients developed dose-limiting grade 3 immune-mediated colitis that led to the definition of the maximum tolerated dose (MTD)...
2018: Oncoimmunology
Fabian V Filipp, Stanca Birlea, Marcus W Bosenberg, Douglas Brash, Pamela B Cassidy, Suzie Chen, John A D'Orazio, Mayumi Fujita, Boon-Kee Goh, Meenhard Herlyn, Arup K Indra, Lionel Larue, Sancy A Leachman, Caroline Le Poole, Feng Liu-Smith, Prashiela Manga, Lluis Montoliu, David A Norris, Yiqun Shellman, Keiran S M Smalley, Richard A Spritz, Richard A Sturm, Susan M Swetter, Tamara Terzian, Kazumasa Wakamatsu, Jeffrey S Weber, Neil F Box
In this perspective, we identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focus on four themes: (1) clinical melanoma research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic pigment cell research, with the goal of outlining current highlights, challenges, and frontiers associated with pigmentation and melanocyte biology...
October 3, 2018: Pigment Cell & Melanoma Research
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