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Interferon melanoma

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https://www.readbyqxmd.com/read/29334492/anti-il-10-mediated-enhancement-of-antitumor-efficacy-of-a-dendritic-cell-targeting-mip3%C3%AE-gp100-vaccine-in-the-b16f10-mouse-melanoma-model-is-dependent-on-type-i-interferons
#1
James T Gordy, Kun Luo, Brian Francica, Charles Drake, Richard B Markham
The chemokine MIP3α (CCL20) binds to CCR6 on immature dendritic cells. Vaccines fusing MIP3α to gp100 have been shown to be effective in therapeutically reducing melanoma tumor burden and prolonging survival in a mouse model. Other studies have provided evidence that interleukin-10 (IL-10) neutralizing antibodies (αIL-10) enhance immunologic melanoma therapies by modulating the tolerogenic tumor microenvironment. In the current study, we have utilized the B16F10 syngeneic mouse melanoma model to demonstrate for the first time that a therapy neutralizing IL-10 enhances the antitumor efficacy of a MIP3α-gp100 DNA vaccine, leading to significantly smaller tumors, slower growing tumors, and overall increases in mouse survival...
January 12, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29331419/the-therapeutic-potential-of-human-adipose-derived-mesenchymal-stem-cells-producing-cxcl10-in-a-mouse-melanoma-lung-metastasis-model
#2
Hamed Mirzaei, Hossein Salehi, Reza Kazemi Oskuee, Ali Mohammadpour, Hamid Reza Mirzaei, Mohammad Reza Sharifi, Reza Salarinia, Hossein Yousofi Darani, Mojgan Mokhtari, Aria Masoudifar, Amirhossein Sahebkar, Rasoul Salehi, Mahmoud Reza Jaafari
Interferon γ-induced protein 10 kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29305520/soluble-slamf6-receptor-induces-strong-cd8-t-cell-effector-function-and-improves-anti-melanoma-activity-in-vivo
#3
Galit Eisenberg, Roni Engelstein, Anat Geiger, Emma Hajaj, Sharon Merims, Shoshana Frankenburg, Ronny Uzana, Abraham Rutenberg, Arthur Machlenkin, Gabi Frei, Tamar Peretz, Michal Lotem
SLAMF6, a member of the SLAM (signaling lymphocyte activation molecules) family, is a homotypic-binding immune receptor expressed on NK, T, and B lymphocytes. Phosphorylation variance between T-cell subclones prompted us to explore its role in anti-melanoma immunity. Using a 203-amino acid sequence of the human SLAMF6 (seSLAMF6) ectodomain, we found that seSLAMF6 reduced activation-induced cell death and had an anti-apoptotic effect on tumor infiltrating lymphocytes. CD8+ T cells costimulated with seSLAMF6 secreted more interferon gamma and displayed augmented cytolytic activity...
January 5, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29301958/a-major-chromatin-regulator-determines-resistance-of-tumor-cells-to-t-cell-mediated-killing
#4
Deng Pan, Aya Kobayashi, Peng Jiang, Lucas Ferrari de Andrade, Rong En Tay, Adrienne Luoma, Daphne Tsoucas, Xintao Qiu, Klothilda Lim, Prakash Rao, Henry W Long, Guo-Cheng Yuan, John Doench, Myles Brown, Shirley Liu, Kai W Wucherpfennig
Many human cancers are resistant to immunotherapy for reasons that are poorly understood. We used a genome-scale CRISPR/Cas9 screen to identify mechanisms of tumor cell resistance to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. Inactivation of >100 genes sensitized mouse B16F10 melanoma cells to killing by T cells, including Pbrm1, Arid2 and Brd7, which encode components of the PBAF form of the SWI/SNF chromatin remodeling complex. Loss of PBAF function increased tumor cell sensitivity to interferon-γ, resulting in enhanced secretion of chemokines that recruit effector T cells...
January 4, 2018: Science
https://www.readbyqxmd.com/read/29249519/a-preliminary-immunohistochemical-study-of-signal-transducer-and-activator-of-transcription-stat-proteins-in-primary-oral-malignant-melanoma
#5
Nikolaos G Nikitakis, Ioannis Gkouveris, Erofili Papadopoulou, Argyrios Daskalopoulos, Alexandra Sklavounou
OBJECTIVE: Primary oral malignant melanoma (POMM) is a rare type of malignancy with a very poor prognosis, the molecular pathogenesis of which remains elusive. The aim of this study was to assess the expression status of signal transducer and activator of transcription (STAT) proteins in POMM. STUDY DESIGN: Six POMMs were included in the study. Total protein levels of STAT1, STAT3, and STAT5a, as well as the tyrosine phosphorylated (activated) form of STAT3 (pSTAT3), were assessed immunohistochemically...
November 3, 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/29233972/irf8-dependent-molecular-complexes-control-the-th9-transcriptional-program
#6
Etienne Humblin, Marion Thibaudin, Fanny Chalmin, Valentin Derangère, Emeric Limagne, Corentin Richard, Richard A Flavell, Sandy Chevrier, Sylvain Ladoire, Hélène Berger, Romain Boidot, Lionel Apetoh, Frédérique Végran, François Ghiringhelli
Interferon regulatory factors (IRF) have critical functions in lymphoid development and in immune response regulation. Although many studies have described the function of IRF4 in CD4+ T cells, few have focused on the IRF4 homologue, IRF8. Here, we show that IRF8 is required for Th9 differentiation in vitro and in vivo. IRF8 functions through a transcription factor complex consisting of IRF8, IRF4, PU.1 and BATF, which binds to DNA and boosts Il9 transcription. By contrast, IRF8 deficiency promotes the expression of other genes such as Il4, as IRF8 dimerises with the transcriptional repressor ETV6 and inhibits Il4 expression...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29207132/irf3-signaling-pathway-serves-an-important-role-in-poly-i-c-induced-procollagen-reduction-in-human-skin-fibroblasts
#7
Cheng Yao, Sangbum Han, Chi-Hyun Park, Ye-Ji Kim, Dong Hun Lee, Jin Ho Chung
Pattern recognition receptors (PRRs) are part of the immune system. They can recognize pathogen‑associated molecular patterns (PAMPs). Toll‑like receptors (TLRs) and retinoic acid‑inducible gene 1 (RIG‑1)‑like receptors (RLRs) are 2 types of PRR in the innate immune system. Double‑stranded RNA (dsRNA) can exist as a PAMP, including dsRNA viruses. dsRNA is known as a ligand not only for TLR3 but also for RLRs, including melanoma differentiation‑associated gene 5 and RIG‑1. Collagen is the main structural protein in the extracellular space in the skin...
November 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29187473/melanoma-of-the-vagina-case-report-and-systematic-review-of-the-literature
#8
Violetta Rapi, Askin Dogan, Beate Schultheis, Franziska Hartmann, Günther A Rezniczek, Clemens B Tempfer
BACKGROUND: Primary melanoma of the vagina (PMV) is a rare entity. The prognosis of women with PMV is poor and there is no standardized therapy for this type of malignancy. We present the case of a 72-year-old woman with PMV (cT2, pN0, M0). CASE REPORT: Imaging studies showed no evidence of regional or distant metastases. Molecular analysis demonstrated wild-type B-Raf proto-oncogene, serine/threonine kinase (BRAF). Staging laparoscopy with pelvic lymphadenectomy and subsequent radiotherapy with 60 Gy delivered as pelvic teletherapy and vaginal brachytherapy was applied...
December 2017: Anticancer Research
https://www.readbyqxmd.com/read/29187401/delivering-type-i-interferon-to-dendritic-cells-empowers-tumor-eradication-and-immune-combination-treatments
#9
Anje Cauwels, Sandra Van Lint, Franciane Paul, Genevieve Garcin, Stefaan De Koker, Alexander Van Parys, Thomas Wueest, Sarah Gerlo, José Van der Heyden, Yann Bordat, Dominiek Catteeuw, Elke Rogge, Annick Verhee, Bart Vandekerckhove, Niko Kley, Gilles Uzé, Jan Tavernier
An ideal generic cancer immunotherapy should mobilize the immune system to destroy tumor cells without harming healthy cells and remain active in case of recurrence. Furthermore, it should preferably not rely on tumor-specific surface markers, as these are only available in a limited set of malignancies. Despite approval for treatment of various cancers, clinical application of cytokines is still impeded by their multiple toxic side effects. Type I interferon (IFN) has a long history in the treatment of cancer, but its multifaceted activity pattern and complex side effects prevent its clinical use...
November 29, 2017: Cancer Research
https://www.readbyqxmd.com/read/29171409/a-case-of-malignant-melanoma-that-developed-multiple-metastases-after-switching-from-interferon-beta-to-pegylated-interferon-alpha-2b-as-adjuvant-therapy
#10
Takeshi Fukumoto, Susumu Fujiwara, Masanobu Sakaguchi, Masahiro Oka, Chikako Nishigori
No abstract text is available yet for this article.
November 24, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/29166644/cylindromatosis-cyld-a-deubiquitinase-attenuates-inflammatory-signaling-pathways-by-activating-toll-like-receptor-3-in-human-mesangial-cells
#11
Tadaatsu Imaizumi, Ryo Hayakari, Shojiro Watanabe, Tomomi Aizawa, Tomoh Matsumiya, Hidemi Yoshida, Kazushi Tsuruga, Shogo Kawaguchi, Hiroshi Tanaka
BACKGROUND/AIMS: Cylindromatosis (CYLD), a deubiquitinase, negatively regulates nuclear factor-κB in various cells. However, its potential roles in glomerular inflammation remain unclear. Because the activation of the Toll-like receptor 3 (TLR3)/type I interferon (IFN) pathways plays a pivotal role in chronic kidney diseases (CKD), we examined the role of CYLD in the TLR3 signaling in cultured human mesangial cells (MCs). METHODS: We stimulated CYLD-silenced MCs with polyinosinic-polycytidylic acid (poly IC), a synthetic analogue of dsRNA, and studied representative TLR3/IFN-β pathways (i...
November 22, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29162045/serial-pseudoprogression-of-metastatic-malignant-melanoma-in-a-patient-treated-with-nivolumab-a-case-report
#12
Yukinori Ozaki, Junichi Shindoh, Yuji Miura, Hiromichi Nakajima, Ryosuke Oki, Miyuki Uchiyama, Jun Masuda, Keiichi Kinowaki, Chihiro Kondoh, Yuko Tanabe, Tsuyoshi Tanaka, Shusuke Haruta, Masaki Ueno, Shigehisa Kitano, Takeshi Fujii, Harushi Udagawa, Toshimi Takano
BACKGROUND: Pseudoprogression refers to a specific pattern of response sometimes observed in malignant melanoma patients receiving treatment with immune-checkpoint inhibitors. Although cases with pseudoprogression documented once have been reported previously, there have been no case reports yet of pseudoprogression events documented twice during treatment. CASE PRESENTATION: A 55-year-old man underwent surgery for locally advanced esophageal malignant melanoma and received postoperative adjuvant interferon therapy...
November 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29150430/interferon-%C3%AE-signaling-in-melanocytes-and-melanoma-cells-regulates-expression-of-ctla-4
#13
Xuan Mo, Hanghang Zhang, Sarah Preston, Kayla Martin, Bo Zhou, Nish Vadalia, Ana M Gamero, Jonathan Soboloff, Italo Tempera, M Raza Zaidi
CTLA-4 is a cell surface receptor on T cells that functions as an immune checkpoint molecule to enforce tolerance to cognate antigens. Anti-CTLA-4 immunotherapy is highly effective at reactivating T cell responses against melanoma, which is postulated to be due to targeting CTLA-4 on T cells. Here we report that CTLA-4 is also highly expressed by most human melanoma cell lines, as well as in normal human melanocytes. Interferon-gamma (IFNG) signaling activated the expression of the human CTLA-4 gene in a melanocyte and melanoma cell-specific manner...
November 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/29136453/randomized-phase-iii-trial-of-adjuvant-therapy-with-locoregional-interferon-beta-versus-surgery-alone-in-stage-ii-iii-cutaneous-melanoma-japan-clinical-oncology-group-study-jcog1309-j-feron
#14
Kenjiro Namikawa, Arata Tsutsumida, Tomonori Mizutani, Taro Shibata, Tatsuya Takenouchi, Shusuke Yoshikawa, Yoshio Kiyohara, Hiroshi Uchi, Masutaka Furue, Dai Ogata, Tetsuya Tsuchida, Naoya Yamazaki
The Dermatologic Oncology Group of Japan Clinical Oncology Group has started a randomized phase III trial to confirm the superiority of adjuvant therapy with locoregional interferon beta in overall survival over surgery alone for patients with pathological stage II/III cutaneous melanoma (JCOG1309). Patients in the interferon beta arm receive intra- or subcutaneous injections of interferon beta directly into the surgical site at a flat dose of 3 million units once per day. Treatment is repeated for 10 consecutive days every 8 weeks for a total of 3 courses during the induction phase, then 1-day injection every 4 weeks for 2...
July 1, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29132350/avian-infectious-bronchitis-virus-disrupts-the-melanoma-differentiation-associated-gene-5-mda5-signaling-pathway-by-cleavage-of-the-adaptor-protein-mavs
#15
Liping Yu, Xiaorong Zhang, Tianqi Wu, Jin Su, Yuyang Wang, Yuexin Wang, Baoyang Ruan, Xiaosai Niu, Yantao Wu
BACKGROUND: Melanoma differentiation associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) selectively sense cytoplasmic viral RNA to induce an antiviral immune response. Infectious bronchitis virus (IBV) is one of the most important infectious agents in chickens, and in chicken cells, it can be recognized by MDA5 to activate interferon production. RIG-I is considered to be absent in chickens. However, the absence of RIG-I in chickens raises the question of whether this protein influences the antiviral immune response against IBV infection...
November 13, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29127039/biodegradable-sting-agonist-nanoparticles-for-enhanced-cancer-immunotherapy
#16
David R Wilson, Rupashree Sen, Joel C Sunshine, Drew M Pardoll, Jordan J Green, Young J Kim
Therapeutic cancer vaccines require adjuvants leading to robust type I interferon and proinflammatory cytokine responses in the tumor microenvironment to induce an anti-tumor response. Cyclic dinucleotides (CDNs), a potent Stimulator of Interferon Receptor (STING) agonist, are currently in phase I trials. However, their efficacy may be limited to micromolar concentrations due to the cytosolic residence of STING in the ER membrane. Here we utilized biodegradable, poly(beta-amino ester) (PBAE) nanoparticles to deliver CDNs to the cytosol leading to robust immune response at >100-fold lower extracellular CDN concentrations in vitro...
November 7, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29116432/seom-clinical-guideline-for-the-management-of-malignant-melanoma-2017
#17
A Berrocal, A Arance, V E Castellon, L de la Cruz, E Espinosa, M G Cao, J L G Larriba, I Márquez-Rodas, A Soria, S M Algarra
All melanoma suspected patients must be confirmed histologically and resected. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon could be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 containing therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 containing therapy...
November 7, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29114547/predictive-factors-of-response-to-immunotherapy-a-review-from-the-spanish-melanoma-group-gem
#18
REVIEW
Enrique Espinosa, Ivan Márquez-Rodas, Ainara Soria, Alfonso Berrocal, Jose Luis Manzano, Maria Gonzalez-Cao, Salvador Martin-Algarra
Immunotherapy has become a key element in the treatment of several tumors, such as lung carcinoma and melanoma. Immunotherapy, unlike classical chemotherapy and targeted drugs, may yield long-term survival, even in patients who stop treatment due to toxicity. This fact has generated considerable excitement and a real shift in the paradigm of cancer treatment. However, only a small subset of patients benefit from immunotherapy. Survival curves show that most patients have progression of the disease in the first months after starting immunotherapy, followed by a slower decrease over the first 3 years, until curves reach a plateau...
October 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29102119/rig-1-and-mda-5-signaling-pathways-contribute-to-ifn-%C3%AE-production-and-viral-replication-in-porcine-circovirus-virus-type-2-infected-pk-15-cells-in-vitro
#19
Bei Huang, Jiansheng Li, Xinchen Zhang, Qiling Zhao, Mingqing Lu, Yingjun Lv
Type I Interferons (IFNs) is known for its antiviral activity; however, it is surprising that in vitro treatment of IFN-α and IFN-γ enhanced the replication of porcine circovirus type 2 (PCV2), indicating a complex relationship between interferon and PCV2. To date, it remains poorly understood how the interferon is produced during PCV2 infection and whether the interferon induced by PCV2 itself can promote viral replication. In this study, PCV2 induced the up-regulation of IFN-β in PK-15 cells, while treatment of PCV2-infected cells with the interferon regulatory factor-3 (IRF3) inhibitor, BX795, decreased the expression of IFN-β, whereas treatment with the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor, BAY11-7082, did not...
November 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/29101107/cytokines-in-cancer-immunotherapy
#20
Thomas A Waldmann
Cytokines that control the immune response were shown to have efficacy in preclinical murine cancer models. Interferon (IFN)-α is approved for treatment of hairy cell leukemia, and interleukin (IL)-2 for the treatment of advanced melanoma and metastatic renal cancer. In addition, IL-12, IL-15, IL-21, and granulocyte macrophage colony-stimulating factor (GM-CSF) have been evaluated in clinical trials. However, the cytokines as monotherapy have not fulfilled their early promise because cytokines administered parenterally do not achieve sufficient concentrations in the tumor, are often associated with severe toxicities, and induce humoral or cellular checkpoints...
November 3, 2017: Cold Spring Harbor Perspectives in Biology
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