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https://www.readbyqxmd.com/read/29737353/induction-of-necrotic-cell-death-and-activation-of-sting-in-the-tumor-microenvironment-via-cationic-silica-nanoparticles-leading-to-enhanced-antitumor-immunity
#1
Myunggi An, Chunsong Yu, Jingchao Xi, Joyce Reyes, Guangzhao Mao, Wei-Zen Wei, Haipeng Liu
Nanotechnology has demonstrated tremendous clinical utility, with potential applications in cancer immunotherapy. Although nanoparticles with intrinsic cytotoxicity are often considered unsuitable for clinical applications, such toxicity may be harnessed in the fight against cancer. Nanoparticle-associated toxicity can induce acute necrotic cell death, releasing tumor-associated antigens which may be captured by antigen-presenting cells to initiate or amplify tumor immunity. To test this hypothesis, cytotoxic cationic silica nanoparticles (CSiNPs) were directly administered into B16F10 melanoma implanted in C57BL/6 mice...
May 8, 2018: Nanoscale
https://www.readbyqxmd.com/read/29735366/self-delivering-rnai-targeting-pd-1-improves-tumor-specific-t-cell-functionality-for-adoptive-cell-therapy-of-malignant-melanoma
#2
Maarten A Ligtenberg, Yago Pico de Coaña, Taisia Shmushkovich, Yuya Yoshimoto, Iva Truxova, Yuan Yang, Monica Betancur-Boissel, Alexey V Eliseev, Alexey D Wolfson, Rolf Kiessling
Adoptive cell therapy (ACT) is becoming a prominent alternative therapeutic treatment for cancer patients relapsing on traditional therapies. In parallel, antibodies targeting immune checkpoint molecules, such as cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) and cell death protein 1 pathway (PD-1), are rapidly being approved for multiple cancer types, including as first line therapy for PD-L1-expressing non-small-cell lung cancer. The combination of ACT and checkpoint blockade could substantially boost the efficacy of ACT...
April 13, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29720400/interferon-regulatory-factor-1-and-a-variant-of-heterogeneous-nuclear-ribonucleoprotein-l-coordinately-silence-the-gene-for-adhesion-protein-ceacam1
#3
Kenneth J Dery, Craig Silver, Lu Yang, John E Shively
The adhesion protein Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is widely expressed in epithelial cells as a short cytoplasmic isoform (S-iso) and in leukocytes as a long cytoplasmic isoform (L-iso) and is frequently silenced in cancer by unknown mechanisms. Previously, we reported that interferon response factor 1 (IRF1) biases alternative splicing (AS) to include the variable exon 7 in CEACAM1, generating L-iso. We now show that IRF1 and a variant of heterogeneous nuclear ribonucleoprotein L (Lv1) coordinately silence the CEACAM1 gene...
May 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29698627/bronchial-mucosal-interferon-%C3%AE-%C3%AE-and-pattern-recognition-receptor-expression-in-experimental-rhinovirus-induced-asthma-exacerbations
#4
Jie Zhu, Simon D Message, Patrick Mallia, Tatiana Kebadze, Marco Contoli, Christine K Ward, Elliot S Barnathan, Mary Ann Mascelli, Onn M Kon, Alberto Papi, Luminita A Stanciu, Michael R Edwards, Peter K Jeffery, Sebastian L Johnston
BACKGROUND: The innate immune system senses viral infection via pattern recognition receptors (PRRs) leading to type I interferon (IFN) production: their roles in rhinovirus (RV)-induced asthma exacerbations in vivo are uncertain. OBJECTIVES: To compare bronchial mucosal type I IFN and PRR expression at baseline and following RV infection in atopic asthmatic and control subjects. METHODS: Immunohistochemistry was used to detect expression of IFN-α, IFN-β and the PRRs, toll-like receptor (TLR)-3, melanoma-differentiation-associated gene-5 (MDA-5) and retinoic-acid-inducible protein-I (RIG-I) in bronchial biopsies from 10 atopic asthmatics and 15 non-asthmatic non-atopic controls at baseline and on day four and six weeks following RV infection...
April 23, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29696308/role-of-mda5-and-interferon-i-in-dendritic-cells-for-t-cell-expansion-by-anti-tumor-peptide-vaccines-in-mice
#5
Hussein Sultan, Juan Wu, Takumi Kumai, Andres M Salazar, Esteban Celis
Cytotoxic T lymphocytes (CTLs) are effective components of the immune system capable of destroying tumor cells. Generation of CTLs using peptide vaccines is a practical approach to treat cancer. We have previously described a peptide vaccination strategy that generates vast numbers of endogenous tumor-reactive CTLs after two sequential immunizations (prime-boost) using poly-ICLC adjuvant, which stimulates endosomal toll-like receptor 3 (TLR3) and cytoplasmic melanoma differentiation antigen 5 (MDA5). Dendritic cells (DCs) play an important role not only in antigen presentation but are critical in generating costimulatory cytokines that promote CTL expansion...
April 25, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29686409/vibrio-vulnificus-quorum-sensing-molecule-cyclo-phe-pro-inhibits-rig-i-mediated-antiviral-innate-immunity
#6
Wooseong Lee, Seung-Hoon Lee, Minwoo Kim, Jae-Su Moon, Geon-Woo Kim, Hae-Gwang Jung, In Hwang Kim, Ji Eun Oh, Hi Eun Jung, Heung Kyu Lee, Keun Bon Ku, Dae-Gyun Ahn, Seong-Jun Kim, Kun-Soo Kim, Jong-Won Oh
The recognition of pathogen-derived ligands by pattern recognition receptors activates the innate immune response, but the potential interaction of quorum-sensing (QS) signaling molecules with host anti-viral defenses remains largely unknown. Here we show that the Vibrio vulnificus QS molecule cyclo(Phe-Pro) (cFP) inhibits interferon (IFN)-β production by interfering with retinoic-acid-inducible gene-I (RIG-I) activation. Binding of cFP to the RIG-I 2CARD domain induces a conformational change in RIG-I, preventing the TRIM25-mediated ubiquitination to abrogate IFN production...
April 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29675108/increased-aurka-gene-copy-number-correlates-with-poor-prognosis-and-predicts-the-efficacy-of-high-dose-interferon-therapy-in-acral-melanoma
#7
Junya Yan, Jiayi Yu, Xiaowen Wu, Tianxiao Xu, Huan Yu, Jie Dai, Meng Ma, Huan Tang, Longwen Xu, Zhihong Chi, Lu Si, Xinan Sheng, Chuanliang Cui, Yan Kong, Jun Guo
Background: AURKA kinase is an essential serine/threonine kinase for mitosis and chromosome stability. The aberrant amplification and overexpression of AURKA are commonly observed in various types of cancer, including cutaneous melanoma. However, the status and the clinical significance of AURKA copy number (CN) in acral melanoma (AM) have not been fully elucidated. Methods: Four hundred and seventy-two AM samples were included in the study. AURKA CN was examined using the QuantiGenePlex DNA Assay. We analysed the relationship of AURKA CN to clinicopathological characteristics and survival of patients with AM...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29658011/a-listeria-derived-polypeptide-promotes-in-vivo-activation-of-nk-cells-for-antitumor-therapy
#8
Amber L Ortiz, Laurel L Lenz
Immunotherapies have shown promise in treatment of cancer, but more potent and targeted therapies are needed. Natural killer (NK) cells are lymphocytes with innate ability to recognize and lyse tumor cells. When activated, they also produce type II interferon (IFNγ) to orchestrate the activity of other immune cells. Strategies to elicit NK cell activation in vivo have potential usefulness in anti-tumor immunotherapies. Here, we report on a strategy to stimulate NK cell activation and anti-tumor activity in mice with established B16...
June 1, 2017: ImmunoHorizons
https://www.readbyqxmd.com/read/29618829/the-genetic-diversity-within-the-1-4-kb-hla-g-5-upstream-regulatory-region-moderately-impacts-on-cellular-microenvironment-responses
#9
Fabrício C Dias, Bruna C Bertol, Isabelle Poras, Bruno M Souto, Celso T Mendes-Junior, Erick C Castelli, Laure Gineau, Audrey Sabbagh, Nathalie Rouas-Freiss, Edgardo D Carosella, Eduardo A Donadi, Philippe Moreau
The HLA-G 5'URR extending 1.4 kb from the ATG presents a unique set of regulatory elements among HLA genes. Several variable sites have been described that coincide with or are close to these elements, thus HLA-G 5'URR polymorphism might influence the HLA-G expression level. We cloned the ten most frequent HLA-G 5'URR haplotypes to evaluate their activity on a luciferase reporter gene in HLA-G+ cell lines (JEG-3/choriocarcinoma and FON+ /melanoma). We also investigated associations between the plasma HLA-G (sHLA-G) levels and the HLA-G 5'URR variability in 157 healthy individuals...
April 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29618619/prevalent-homozygous-deletions-of-type-i-interferon-and-defensin-genes-in-human-cancers-associate-with-immunotherapy-resistance
#10
Liguo Wang, Zhenqing Ye, Haidong Dong, Ying Li, Tao Ma, Haojie Huang, Hon S Leong, Jeanette E Eckel-Passow, Jean-Pierre Kocher, Han Liang
PURPOSE: Homozygous deletions play important roles in carcinogenesis. The genome-wide screening for homozygously deleted genes in many different cancer types with a large number of patient specimens representing the tumor heterogeneity has not been done. EXPERIMENTAL DESIGN: We performed integrative analyses of the copy number profiles of 10,759 patients across 31 cancer types from The Cancer Genome Atlas project. RESULTS: We found that the Type-I interferon, α- and β-defensin genes were homozygously deleted in 19 cancer types with high frequencies (7%-31%, median = 12%; interquartile range = 10-16...
April 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29600494/duox2-induced-innate-immune-responses-in-the-respiratory-epithelium-and-intranasal-delivery-of-duox2-dna-using-polymer-that-mediates-immunization
#11
REVIEW
Yung Jin Jeon, Hyun Jik Kim
Respiratory mucosa especially nasal epithelium is well known as the first-line barrier of air-borne pathogens. High levels of reactive oxygen species (ROS) are detected in in vitro cultured human epithelial cells and in vivo lung. With identification of NADPH oxidase (Nox) system of respiratory epithelium, the antimicrobial role of ROS has been studied. Duox2 is the most abundant Nox isoform and produces the regulated amount of ROS in respiratory epithelium. Duox2-derived ROS are involved in antiviral innate immune responses but more studies are needed to verify the mechanism...
March 30, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29581905/antiphospholipid-antibody-induced-by-nivolumab
#12
Ahmed Aburahma, Nour Aljariri Alhesan, Farah Elounais, Emad Abu Sitta
Nivolumab is a monoclonal antibody against the programmed death protein 1 and is used for patients with advanced melanoma. It is associated with potentially immune-related adverse events, including disorders of the skin, GI tract, and the thyroid; these disorders were successfully treated with prednisone and infliximab. Other immunotherapeutic agents were observed to induce the formation of antiphospholipid antibody (APA) including α -interferon and interleukin-2. We present a case of APA development after the third dose of nivolumab in a 71-year-old male with advanced melanoma...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29556352/the-enhanced-antitumor-specific-immune-response-with-mannose-and-cpg-odn-coated-liposomes-delivering-trp2-peptide
#13
Chunhui Lai, Siliang Duan, Fang Ye, Xiaoqiong Hou, Xi Li, Jin Zhao, Xia Yu, Zixi Hu, Zhuoran Tang, Fengzhen Mo, Xiaomei Yang, Xiaoling Lu
PURPOSE: Dendritic cell (DC)-based cancer vaccines is a newly emerging and potent form of immune therapy. As for any new technology, there are still considerable challenges that need to be addressed. Here, we investigate the antitumor potential of a novel liposomal vaccine, M/CpG-ODN-TRP2-Lipo. METHODS: We developed a vaccination strategy by assembling the DC-targeting mannose and immune adjuvant CpG-ODN on the surface of liposomes, which were loaded with melanoma-specific TRP2180-188 peptide as liposomal vaccine...
2018: Theranostics
https://www.readbyqxmd.com/read/29553967/traf3-interacting-protein-3-a-new-oncotarget-promotes-tumor-growth-in-melanoma
#14
Patrick Nasarre, Ingrid V Bonilla, John S Metcalf, Eleanor G Hilliard, Nancy Klauber-DeMore
TRAF3-interacting protein 3 (TRAF3IP3) is expressed in the immune system and participates in cell maturation, tissue development, and immune response. In a previous study, we reported that TRAF3IP3 levels were substantially increased in the vasculature of breast cancer tissues, suggesting a proangiogenic role. In this study, we investigated TRAF3IP3 tumorigenic function. TRAF3IP3 protein was present in several cancer cell lines, with highest levels in melanoma. In addition, tumor microarray analysis on 23 primary melanoma and nine positive lymph nodes revealed that 70% of human primary melanoma and 66% of lymph node metastases were positive for TRAF3IP3...
March 16, 2018: Melanoma Research
https://www.readbyqxmd.com/read/29551126/role-of-mda-7-il-24-a-multifunction-protein-in-human-diseases
#15
Mitchell E Menezes, Praveen Bhoopathi, Anjan K Pradhan, Luni Emdad, Swadesh K Das, Chunqing Guo, Xiang-Yang Wang, Devanand Sarkar, Paul B Fisher
Subtraction hybridization identified genes displaying differential expression as metastatic human melanoma cells terminally differentiated and lost tumorigenic properties by treatment with recombinant fibroblast interferon and mezerein. This approach permitted cloning of multiple genes displaying enhanced expression when melanoma cells terminally differentiated, called melanoma differentiation associated (mda) genes. One mda gene, mda-7, has risen to the top of the list based on its relevance to cancer and now inflammation and other pathological states, which based on presence of a secretory sequence, chromosomal location, and an IL-10 signature motif has been named interleukin-24 (MDA-7/IL-24)...
2018: Advances in Cancer Research
https://www.readbyqxmd.com/read/29543704/three-antigen-loading-methods-in-dendritic-cell-vaccines-for-metastatic-melanoma
#16
Larisa J Geskin, James J Damiano, Christina C Patrone, Lisa H Butterfield, John M Kirkwood, Louis D Falo
In the current era of checkpoint inhibitors, some patients with metastatic melanoma have shown a significant improvement in survival. However, optimization of immunotherapy is an ongoing effort. Monocyte-derived dendritic cell (MODC) vaccines have been shown in clinical trials to be safe and capable of inducing tumor-specific immunity as well as occasional objective clinical responses. Here, we conducted a three-arm pilot clinical study in 15 patients with metastatic melanoma to evaluate three types of MODC vaccines, differing only by strategies of tumor antigen delivery...
June 2018: Melanoma Research
https://www.readbyqxmd.com/read/29541462/multidisciplinary-therapy-for-metastatic-primary-malignant-melanoma-of-the-esophagus-a-case-report
#17
Ken Sasaki, Yasuto Uchikado, Itaru Omoto, Masahiko Amatatsu, Koichi Megumi, Hiroshi Okumura, Kosei Maemura, Shoji Natsugoe
Standard treatment strategies have not yet been established for primary malignant melanoma of the esophagus (PMME), and far much less for recurrent disease. There are no reports of anti-programmed death-1 antibody treatment of recurrent PMME. A 60-year-old Japanese man was diagnosed with a primary malignant melanoma in the lower esophagus. The patient underwent mediastinoscope-assisted subtotal esophagectomy, and two nodal involvements were detected in the lymph nodes (LN)s along the left gastric artery. Paclitaxel and oral fluoropyrimidine were administered for 2 months as adjuvant treatment based on results of a histoculture drug response assay...
April 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29538091/lymphoid-aggregates-in-desmoplastic-melanoma-have-features-of-tertiary-lymphoid-structures
#18
Anne M Stowman, Alexandra W Hickman, Ileana S Mauldin, Adela Mahmutovic, Alejandro A Gru, Craig L Slingluff
Desmoplastic melanomas (DM) have unique and challenging clinical presentations and histomorphology. A characteristic feature is the presence of scattered lymphoid aggregates. However, the nature of these aggregates is not defined. We hypothesized that they may be tertiary lymphoid structures (TLS), and may be associated with programmed death ligand 1 (PD-L1) expression. We searched our tissue database for 'pure' DMs and for scars as control tissues, collected clinical information, and reviewed H&E histology...
June 2018: Melanoma Research
https://www.readbyqxmd.com/read/29521881/combination-immunotherapies-implementing-adoptive-t-cell-transfer-for-advanced-stage-melanoma
#19
Kendra C Foley, Michael I Nishimura, Tamson V Moore
Immunotherapy is a promising method of treatment for a number of cancers. Many of the curative results have been seen specifically in advanced-stage melanoma. Despite this, single-agent therapies are only successful in a small percentage of patients, and relapse is very common. As chemotherapy is becoming a thing of the past for treatment of melanoma, the combination of cellular therapies with immunotherapies appears to be on the rise in in-vivo models and in clinical trials. These forms of therapies include tumor-infiltrating lymphocytes, T-cell receptor, or chimeric antigen receptor-modified T cells, cytokines [interleukin (IL-2), IL-15, IL-12, granulocyte-macrophage colony stimulating factor, tumor necrosis factor-α, interferon-α, interferon-γ], antibodies (αPD-1, αPD-L1, αTIM-3, αOX40, αCTLA-4, αLAG-3), dendritic cell-based vaccines, and chemokines (CXCR2)...
June 2018: Melanoma Research
https://www.readbyqxmd.com/read/29512705/interferon-regulatory-factor-3-mediates-poly-i-c-induced-innate-immune-response-and-apoptosis-in-non%C3%A2-small-cell-lung-cancer
#20
Liang Yi, Dan Sun, Qian Han, Zhonghui Liu, Zeng Zeng, Yanping Wu, Xiaoyu Chai, Xinmin Liu
Immunotherapy is considered one of the most promising treatments for lung cancer. The cell signalling molecules melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene I protein (RIG‑I) are essential receptors that recognise intracellular pathogen-associated nucleic acids, whereas interferon regulatory factor 3 (IRF3) controls the expression of innate immunity-associated genes in macrophages. However, the innate immune response to polyinosinic:polycytidylic acid [Poly(I:C)] in lung cancer remains to be elucidated...
March 5, 2018: International Journal of Oncology
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