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Interferon melanoma

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https://www.readbyqxmd.com/read/28738020/resident-memory-t-cells-in-the-skin-mediate-durable-immunity-to-melanoma
#1
Brian T Malik, Katelyn T Byrne, Jennifer L Vella, Peisheng Zhang, Tamer B Shabaneh, Shannon M Steinberg, Aleksey K Molodtsov, Jacob S Bowers, Christina V Angeles, Chrystal M Paulos, Yina H Huang, Mary Jo Turk
Tissue-resident memory T (TRM) cells have been widely characterized in infectious disease settings; however, their role in mediating immunity to cancer remains unknown. We report that skin-resident memory T cell responses to melanoma are generated naturally as a result of autoimmune vitiligo. Melanoma antigen-specific TRM cells resided predominantly in melanocyte-depleted hair follicles and were maintained without recirculation or replenishment from the lymphoid compartment. These cells expressed CD103, CD69, and CLA (cutaneous lymphocyte antigen), but lacked PD-1 (programmed cell death protein-1) or LAG-3 (lymphocyte activation gene-3), and were capable of making IFN-γ (interferon-γ)...
April 14, 2017: Science Immunology
https://www.readbyqxmd.com/read/28727675/type-1-diabetes-mellitus-caused-by-treatment-with-low-dose-interferon-%C3%AE-in-a-melanoma-patient
#2
Daniel Sossau, Lukas Kofler, Thomas Eigentler
Interferon-α (INF-α) is used as an adjuvant treatment for high-risk cutaneous melanoma. It has a large variety of potentially severe and irreversible side effects and can contribute toward the development of autoimmune disease. We report a case of a 59-year-old woman who developed type 1 diabetes following the use of low-dose IFN-α for the adjuvant treatment of stage IIB melanoma. Fifteen months after initiating IFN-α, she presented with blood glucose of 1126 mg/dl, hyponatremia, and microalbuminuria...
July 19, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28723893/in-vivo-crispr-screening-identifies-ptpn2-as-a-cancer-immunotherapy-target
#3
Robert T Manguso, Hans W Pope, Margaret D Zimmer, Flavian D Brown, Kathleen B Yates, Brian C Miller, Natalie B Collins, Kevin Bi, Martin W LaFleur, Vikram R Juneja, Sarah A Weiss, Jennifer Lo, David E Fisher, Diana Miao, Eliezer Van Allen, David E Root, Arlene H Sharpe, John G Doench, W Nicholas Haining
Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade. We recovered the known immune evasion molecules PD-L1 and CD47, and confirmed that defects in interferon-γ signalling caused resistance to immunotherapy...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28710916/systemic-immune-inflammation-index-and-circulating-t-cell-immune-index-predict-outcomes-in-high-risk-acral-melanoma-patients-treated-with-high-dose-interferon
#4
Jiayi Yu, Xiaowen Wu, Huan Yu, Siming Li, LiLi Mao, Zhihong Chi, Lu Si, Xinan Sheng, Chuanliang Cui, Jie Dai, Meng Ma, Huan Tang, Tianxiao Xu, Junya Yan, Yan Kong, Jun Guo
High-dose interferon alfa-2b (IFN-α-2b) improves the survival of patients with high-risk melanoma. We aimed to identify baseline peripheral blood biomarkers to predict the outcome of acral melanoma patients treated with IFN-α-2b. Pretreatment baseline parameters and clinical data were assessed in 226 patients with acral melanoma. Relapse-free survival (RFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and multivariate Cox regression analyses were applied after adjusting for stage, lactate dehydrogenase (LDH), and ulceration...
July 12, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28706591/interferon-related-pericarditis-review
#5
Kazuaki Nishio, Tsutomu Arase, Hiroko Tada, Hideaki Tachibana
AIM: To conduct a review of "interferon related pericarditis". METHODS: We searched MEDLINE, EMBASE, Cinahl, and the Cochrane Database from the earliest available date through September 2016. A search strategy using the Medical Subject Headings and text keywords "interferon" and "pericarditis" were used. RESULTS: Nine case reports were eligible for the present study. Six of 8 cases were women and the mean age was 43.8 ± 13.8 years with chronic hepatitis C in 6 cases, malignant melanoma in 2 cases and chronic myelogenous leukemia in 1 case...
June 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/28697228/lichenoid-dermatitis-from-interferon-alpha-2a-in-a-patient-with-metastatic-renal-cell-carcinoma-and-seronegative-hcv
#6
Amelia E Bush, Sharon R Hymes, Sirunya Silapunt
<p>Cutaneous reactions to interferon, including a lichenoid drug reaction, are most commonly reported in patients undergoing treatment for hepatitis C virus (HCV) infection. There have been case reports of interferon-induced lichen planus in seronegative HCV patients with lymphoproliferative disorders and melanoma. We report the case of a 71-year-old man undergoing treatment with interferon for metastatic renal cell carcinoma (RCC) who developed an eruption 2 months after starting interferon. Clinical and histological findings from biopsies supported a diagnosis of interferon-induced lichen planus...
July 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28692949/adjuvant-interferon-%C3%AE-for-the-treatment-of-high-risk-melanoma-an-individual-patient-data-meta-analysis
#7
REVIEW
Natalie J Ives, Stefan Suciu, Alexander M M Eggermont, John Kirkwood, Paul Lorigan, Svetomir N Markovic, Claus Garbe, Keith Wheatley
BACKGROUND: Many randomised trials assessing interferon-α (IFN-α) as adjuvant therapy for high-risk malignant melanoma have been undertaken. To better assess the role of IFN-α, an individual patient data (IPD) meta-analysis of these trials was undertaken. METHODS: IPD was sought from all randomised trials of adjuvant IFN-α versus no IFN-α for high-risk melanoma. Primary outcomes were event-free survival (EFS) and overall survival (OS). Standard methods for quantitative IPD meta-analysis were used...
July 7, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28690075/tumor-microenvironment-changes-leading-to-resistance-of-immune-checkpoint-inhibitors-in-metastatic-melanoma-and-strategies-to-overcome-resistance
#8
REVIEW
Bhargavi Pulluri, Abhijeet Kumar, Montaser Shaheen, Joanne Jeter, Srinath Sundararajan
Immunotherapy with checkpoint inhibitors targeting CTLA-4 and/or PD-1 receptors independent of the BRAF mutational status and targeted therapy with BRAF and MEK inhibitors in BRAF V600 mutated patients have taken the forefront of advanced melanoma treatment. The main advantage of immunotherapy is its ability to provide durable responses in a subset of patients. However, significant proportions of patients either do not respond or have progression after initial response to immunotherapies. Multiple changes in the tumor microenvironment, such as down regulation of immune checkpoint ligands by tumor, alteration in interferon signaling, and activation of alternate immune suppressive pathways, have been identified as possible reasons for failure of immune checkpoint therapy...
July 6, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28680742/modulation-of-mhc-class-i-surface-expression-in-b16f10-melanoma-cells-by-methylseleninic-acid
#9
Claudia Lennicke, Jette Rahn, Jürgen Bukur, Falko Hochgräfe, Ludger A Wessjohann, Rudolf Lichtenfels, Barbara Seliger
The essential trace element selenium (Se) might play a role in cancer prevention as well as for cancer therapy. Its metabolite methylselenol is able to kill cells through distinct mechanisms including induction of reactive oxygen species, DNA damage and apoptosis. Since methylselenol affects innate immune responses by modulating the expression of NKG2D ligands, the aim of this study was to determine whether the methylselenol generating compound methylseleninic acid (MSA) influences the expression of the MHC class I surface antigens and growth properties thereby reverting immune escape...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679751/aim2-like-receptors-positively-and-negatively-regulate-the-interferon-response-induced-by-cytosolic-dna
#10
Yuki Nakaya, Jingtao Lilue, Spyridon Stavrou, Eileen A Moran, Susan R Ross
Cytosolic DNAs derived from retrotransposons serve as pathogen-associated molecular patterns for pattern recognition receptors (PRRs) that stimulate the induction of interferons (IFNs) and other cytokines, leading to autoimmune disease. Cyclic GMP-AMP synthase is one PRR that senses retrotransposon DNA, activating type I IFN responses through the stimulator of IFN genes (STING). Absent in melanoma 2 (AIM2)-like receptors (ALRs) have also been implicated in these pathways. Here we show that the mouse ALR IFI205 senses cytosolic retrotransposon DNA independently of cyclic GMP-AMP production...
July 5, 2017: MBio
https://www.readbyqxmd.com/read/28669340/oncolytic-tanapoxvirus-expressing-interleukin-2-is-capable-of-inducing-the-regression-of-human-melanoma-tumors-in-the-absence-of-t-cells
#11
Tiantian Zhang, Dennis H Kordish, Yogesh R Suryawanshi, Rob R Eversole, Steven Kohler, Charles D Mackenzie, Karim Essani
Oncolytic viruses (OVs), which preferentially infect cancer cells and induce host anti-tumor immune responses, have emerged as an effective melanoma therapy. Tanapoxvirus (TANV), which possesses a large genome and causes mild self-limiting disease in humans, is potentially an ideal OV candidate. Interleukin-2 (IL-2), a T-cell growth factor, plays a critical role in activating T cells, natural killer (NK) cells and macrophages in both the innate and adaptive immune system. In this study, a recombinant TANV expressing mouse IL-2 (TANVΔ66R/mIL-2) was generated, where the viral thymidine kinase (TK) gene (66R) was replaced with the mIL-2 transgene...
June 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28659477/west-nile-virus-ns1-antagonizes-interferon-%C3%AE-production-by-targeting-rig-i-and-mda5
#12
Hong-Lei Zhang, Han-Qing Ye, Si-Qing Liu, Cheng-Lin Deng, Xiao-Dan Li, Pei-Yong Shi, Bo Zhang
West Nile virus (WNV) is a mosquito-borne flavivirus that causes epidemics of encephalitis and viscerotropic disease worldwide. This virus has spread rapidly and has posed significant a public health threat since the outbreak in New York City in 1999. The interferon (IFN)-mediated antiviral response represents an important component of virus-host interactions and plays an essential role in regulating viral replication. Previous studies have suggested that multifunctional non-structural proteins encoded by flaviviruses antagonize the host IFN response via various means in order to establish efficient viral replication...
June 28, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28651122/activation-of-irf3-contributes-to-ifn-%C3%AE-and-isg54-expression-during-the-immune-responses-to-b16f10-tumor-growth
#13
Zachary Guinn, Deborah M Brown, Thomas M Petro
Interferon Regulatory Factor (IRF-3) has been shown to contribute to immune control of B16 melanoma tumor growth. We have shown previously that IRF-3 has a role in IFN-γ-induced expression of pro-apoptotic interferon stimulated gene 54 (ISG54) in macrophages and IFN-γ in T cells. To investigate the IRF3-IFN-γ-ISG54 nexus, we injected C57Bl/6 (B6) and IRF3KO mice s.c. with luciferase-producing B16-F10 tumor cells. Tumor growth as measured by luciferase levels was similar between B6 and IRF3KO mice at days 2 and 6, but was significantly greater at day 9 in IRF3KO mice compared with B6 mice...
June 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28649738/adjuvant-therapy-with-low-dose-interferon-beta-for-stage-ii-and-iii-melanoma-results-of-a-retrospective-analysis
#14
T Yanagi, H Hata, E Homma, S Kitamura, K Imafuku, H Shimizu
Interferon (IFN)-alfa as an adjuvant therapy has been found to improve relapse-free survival in patients with malignant melanoma (MM). However, the efficacy of IFN-beta has not been studied in detail. This study evaluated the contribution of adjuvant IFN-beta therapy to improvements in the prognosis of patients with MM. We reviewed 63 patients with resected stage II/III primary MM at our institution. Of these, 36 had been treated with IFN-beta adjuvant therapy (subcutaneous injection, 3 × 10(6) IU/day, 10 days), while 27 patients had undergone observation alone...
June 25, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28639716/expression-of-the-autoantigen-trim33-tif1%C3%AE-in-skin-and-muscle-of-patients-with-dermatomyositis-is-upregulated-together-with-markers-of-cellular-stress
#15
B Scholtissek, S Ferring-Schmitt, J Maier, J Wenzel
Dermatomyositis (DM) is an autoimmune disorder associated with a dysregulation of immune homeostasis of both the innate and adaptive immune system. Earlier data suggested that these two arms of the immune system interconnect in DM. In the current study, we analysed the association of autoantigen expression [adaptive system components: Mi2, transcriptional intermediary factor (TIF)1γ, small ubiquitin-like modifier 1 activating enzyme subunit (SAE)1, melanoma differentiation-associated protein (MDA)5] with markers of cellular stress (innate system components: MxA, p53) in skin and muscle (immunohistology and gene expression data, respectively)...
August 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28627943/the-efficacy-and-safety-of-adjuvant-interferon-alfa-therapy-in-the-evolving-treatment-landscape-for-resected-high-risk-melanoma
#16
Van Anh Trinh, Chrystia Zobniw, Wen-Jen Hwu
Patients with resected stage II or III melanoma are at high risk of recurrence, with 5-year mortality rate of 40-60%. Adjuvant interferon-alfa has demonstrated a small RFS and OS benefit versus observation in this patient population. However, the adjuvant treatment landscape is evolving rapidly. Areas covered: This review aims to summarize the safety and efficacy profiles of adjuvant IFNα/PEG-IFNα, revisit the controversy surrounding its application, and reappraise its position in the rapidly changing treatment landscape of resected melanoma...
June 30, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28620382/phase-ii-study-of-adjuvant-immunotherapy-with-the-csf-470-vaccine-plus-bacillus-calmette-guerin-plus-recombinant-human-granulocyte-macrophage-colony-stimulating-factor-vs-medium-dose-interferon-alpha-2b-in-stages-iib-iic-and-iii-cutaneous-melanoma-patients
#17
José Mordoh, María Betina Pampena, Mariana Aris, Paula Alejandra Blanco, Mónica Lombardo, Erika María von Euw, Soledad Mac Keon, Michelle Yépez Crow, Alicia Inés Bravo, Juan Manuel O'Connor, Ana Gabriela Orlando, Franco Ramello, Estrella Mariel Levy, María Marcela Barrio
The irradiated, allogeneic, cellular CSF-470 vaccine plus Bacillus Calmette-Guerin (BCG) and recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) is being tested against medium-dose IFN-α2b in stages IIB-III cutaneous melanoma (CM) patients (pts) after surgery in an open, randomized, Phase II/III study. We present the results of the Phase II part of the ongoing CASVAC-0401 study (ClinicalTrials.gov: NCT01729663). Thirty-one pts were randomized to the CSF-470 vaccine (n = 20) or to the IFN-α2b arm (n = 11)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28613357/optical-coherence-tomography-angiography-in-the-multimodal-imaging-evaluation-of-interferon-associated-retinopathy-a-case-report
#18
Leonardo Mastropasqua, Enrico Borrelli, Francesco Amodei, Agbeanda Aharrh-Gnama, Lisa Toto, Peter A Mattei, Rodolfo Mastropasqua
The authors present the case of a 59-year-old woman in treatment with interferon alfa-2b for stage IV melanoma and widespread metastases who presented with interferon-associated retinopathy. An ocular examination revealed multiple retinal cotton-wool spots and hard exudates. Interferon treatment was suspended. The patient was followed up for 5 months following the baseline visit by means of en face optical coherence tomography (OCT), spectral-domain OCT, and OCT angiography. Multimodal imaging was useful in the follow-up of this condition, permitting the characterization of all the lesions hallmarking the interferon-retinopathy and showing that this illness was related to a reduction of the retinal vascular perfusion...
June 1, 2017: Ophthalmic Surgery, Lasers & Imaging Retina
https://www.readbyqxmd.com/read/28604143/combinatorial-antitumor-effects-of-indoleamine-2-3-dioxygenase-inhibitor-nlg919-and-paclitaxel-in-a-murine-b16-f10-melanoma-model
#19
Xiangjing Meng, Guangying Du, Liang Ye, Shanyue Sun, Qiaofeng Liu, Hongbo Wang, Wenyan Wang, Zimei Wu, Jingwei Tian
Indoleamine 2,3-dioxygenase (IDO) is involved in tumor immune escape and resistance to chemotherapy, and is clinically correlated with tumor progression. IDO inhibitors show marginal efficacy as single agents; therefore, combinations of these inhibitors with other therapies hold promise for cancer therapy. The aim of this study was to investigate the synergistic antitumor effects of IDO inhibitor NLG919 in combination with different regimens of paclitaxel in a murine B16-F10 melanoma model. NLG919 increased the cytotoxic activity of paclitaxel toward B16-F10 cells in the presence of pretreatment with interferon (IFN)-γ in vitro...
June 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28597059/-malignant-melanoma-of-the-urinary-bladder
#20
REVIEW
T Otto, D Barski, R Bug
Primary malignant melanoma of the genitourinary tract is a rare lesion. We report the case of a 52-year-old man with primary manifestation of metastatic melanoma in the bladder. Multimodal therapy with transurethral tumor resection and systemic interferon/dacarbazine was not successful and the patient died 18 months later. Currently immune checkpoint inhibitors, CTLA-4 (cytotoxic T lymphocyte antigen-4) and PD-L1 are currently being tested in phase III studies and show long-lasting response in the case of classical melanoma manifestations...
July 2017: Der Urologe. Ausg. A
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