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Hiroshi Okabe, Hiroaki Hata, Hisahiro Hosogi, Shugo Ueda, Shuji Ota, Yousuke Kinjo, Nobuaki Hoshino, Shigeo Hisamori, Shigeru Tsunoda, Kazutaka Obama, Yoshiharu Sakai
BACKGROUND: The authors previously showed the significant efficacy of S-1 plus cisplatin for gastric cancer with limited peritoneal metastasis. They conducted a phase 2 study to evaluate the safety and efficacy of induction chemotherapy using a docetaxel, cisplatin, and S-1 (DCS) triplet regimen to treat gastric cancer with peritoneal metastasis. METHODS: The key eligibility criteria were gastric cancer with peritoneal metastasis or positive peritoneal cytology but no other distant metastases and capability of oral administration...
February 14, 2019: Annals of Surgical Oncology
Long-Shan Ji, Qiu-Tian Gao, Ruo-Wen Guo, Xin Zhang, Zhen-Hua Zhou, Zhuo Yu, Xiao-Jun Zhu, Ya-Ting Gao, Xue-Hua Sun, Yue-Qiu Gao, Man Li
Aim: To compare the clinical efficacy of the combination therapy with Bushen formula (BSF) plus entecavir (ETV) in naïve chronic hepatitis B (CHB) patients and that in CHB patients with partial virological response to ETV and explore the relevant immunoregulatory mechanism. Materials and Methods: Two hundred and twenty CHB patients were enrolled in the historical prospective cohort study. Patients were categorized into a treatment group (T-Group: combination therapy with BSF plus ETV) and a control group (C-Group: ETV)...
2019: Journal of Immunology Research
Hisataka Kobayashi
Near infrared photoimmunotherapy(NIR-PIT)is a new molecularly-targeted cancer photo-therapy based on conjugating a near infrared silica-phthalocyanine dye, IRDye700DX(IR700), to a monoclonal antibody(mAb)targeting cell-surface molecules. NIR-PIT targetingEGFR usingthe cetuximab-IR700 conjugate is now in transition to fast-track global Phase Ⅲ clinical trial in late-stage head and neck squamous cell cancer patients. When exposed to NIR light, the conjugate induces a highlyselective necrotic/immunogenic cell death(ICD)only in target-positive, mAb-IR700-bound cancer cells...
January 2019: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Rashida Ginwala, Raina Bhavsar, DeGaulle I Chigbu, Pooja Jain, Zafar K Khan
Inflammation has been reported to be intimately linked to the development or worsening of several non-infectious diseases. A number of chronic conditions such as cancer, diabetes, cardiovascular disorders, autoimmune diseases, and neurodegenerative disorders emerge as a result of tissue injury and genomic changes induced by constant low-grade inflammation in and around the affected tissue or organ. The existing therapies for most of these chronic conditions sometimes leave more debilitating effects than the disease itself, warranting the advent of safer, less toxic, and more cost-effective therapeutic alternatives for the patients...
February 5, 2019: Antioxidants (Basel, Switzerland)
Dieke van Dinther, Miguel Lopez Venegas, Henrike Veninga, Katarzyna Olesek, Leoni Hoogterp, Mirjam Revet, Martino Ambrosini, Hakan Kalay, Johannes Stöckl, Yvette van Kooyk, Joke M M den Haan
The lack of tumor-reactive T cells is one reason why immune checkpoint inhibitor therapies still fail in a significant proportion of melanoma patients. A vaccination that induces melanoma-specific T cells could potentially enhance the efficacy of immune checkpoint inhibitors. Here, we describe a vaccination strategy in which melanoma antigens are targeted to mouse and human CD169 and thereby induce strong melanoma antigen-specific T cell responses. CD169 is a sialic acid receptor expressed on a subset of mouse splenic macrophages that captures antigen from the blood and transfers it to dendritic cells (DCs)...
February 5, 2019: Cancers
Maud Plantinga, Colin G de Haar, Ester Dünnebach, Denise A M H van den Beemt, Kitty W M Bloemenkamp, Michal Mokry, Jaap Jan Boelens, Stefan Nierkens
Dendritic cells (DCs) are professional antigen-presenting cells which instruct both the innate and adaptive immune systems. Once mature, they have the capacity to activate and prime naïve T cells for recognition and eradication of pathogens and tumor cells. These characteristics make them excellent candidates for vaccination strategies. Most DC vaccines have been generated from ex vivo culture of monocytes (mo). The use of mo-DCs as vaccines to induce adaptive immunity against cancer has resulted in clinical responses but, overall, treatment success is limited...
February 5, 2019: Cancers
Stephen R Thom, Veena M Bhopale, Ming Yang
Hyperbaric oxygen (HBO2 ) became a mainstay for treating decompression sickness (DCS) because bubbles are associated with the disorder. Inflammatory processes including production of circulating microparticles (MPs) have now been shown to occur with DCS, leading to questions regarding pathophysiology and the role for HBO2 . We investigated effects of HBO2 on mice exposed to 790 kPa air pressure for 2 hours, which triggers elevations of MPs ladened with interleukin (IL)-1β that cause diffuse vascular injuries...
February 14, 2019: Journal of Applied Physiology
Fangyuan Zhou, Bing Feng, Haijun Yu, Dangge Wang, Tingting Wang, Yuting Ma, Siling Wang, Yaping Li
Chemoimmunotherapy is reported to activate a robust T cell antitumor immune response by triggering immunogenic cell death (ICD), which has initiated a number of clinical trials. However, current chemoimmunotherapy is restricted to a small fraction of patients due to low drug delivery efficacy and immunosuppression within the tumor microenvironment. A tumor microenvironment-activatable prodrug vesicle for cancer chemoimmunotherapy using ICD is herein reported. The prodrug vesicles are engineered by integrating an oxaliplatin (OXA) prodrug and PEGylated photosensitizer (PS) into a single nanoplatform, which show tumor-specific accumulation, activation, and deep penetration in response to the tumoral acidic and enzymatic microenvironment...
February 14, 2019: Advanced Materials
Liwen Lin, He Xu, Muath Bishawi, FeiFei Feng, Kannan Samy, George Truskey, Andrew S Barbas, Allan D Kirk, Todd V Brennan
The innate immune system is a critical regulator of the adaptive immune responses that lead to allograft rejection. It is increasingly recognized that endogenous molecules released from tissue injury and cell death are potent activators of innate immunity. Mitochondria, ancestrally related to bacteria, possess an array of endogenous innate immune activating molecules. We have recently demonstrated that extracellular mitochondria are abundant in the circulation of deceased organ donors and that their presence correlates with early allograft dysfunction...
February 14, 2019: American Journal of Transplantation
Arthur Baruel Zaneti, Marcio Massao Yamamoto, Fernando Bandeira Sulczewski, Bianca da Silva Almeida, Higo Fernando Santos Souza, Natália Soares Ferreira, Denicar Lina Nascimento Fabris Maeda, Natiely Silva Sales, Daniela Santoro Rosa, Luís Carlos de Souza Ferreira, Silvia Beatriz Boscardin
Dengue fever has become a global threat, causing millions of infections every year. An effective vaccine against all four serotypes of dengue virus (DENV) has not been developed yet. Among the different vaccination strategies available today, DNA vaccines are safe and practical, but currently induce relatively weak immune responses in humans. In order to improve immunogenicity, antigens may be targeted to dendritic cells (DCs), the main antigen presenting cells and orchestrators of the adaptive immune response, inducing T and B cell activation...
2019: Frontiers in Immunology
Marita Chakhtoura, Robert W Chain, Priscila Y Sato, Connie C Qiu, Michael H Lee, Joseph J Meissler, Toby K Eisenstein, Walter J Koch, Roberto Caricchio, Stefania Gallucci
Attenuating the innate immunity activation could ameliorate inflammation and disease in settings such as transplant rejection or autoimmunity. Recently, a pivotal role for metabolic re-programming in TLR-induced dendritic cell (DC) activation has emerged. Ethyl pyruvate (EP), a pyruvate derivative, possesses anti-inflammatory properties in vitro and in animal models of disease. However, its effects on DCs remain elusive. We found that EP attenuated LPS-induced activation of murine GM-CSF bone marrow-derived dendritic cells (DCs) in vitro , reducing pro-inflammatory cytokine and IL-10 production, costimulatory molecule and MHC expression, the type I Interferon (IFN-I) response, the LPS-induced cell death, and the ability of DCs to stimulate allogeneic T cells...
2019: Frontiers in Immunology
Parisa Kalantari, Stephen C Bunnell, Miguel J Stadecker
Schistosomiasis is a major helminthic disease in which damage to the affected organs is orchestrated by a pathogenic host CD4 T helper (Th) cell-mediated immune response against parasite eggs. In the case of the species Schistosoma mansoni , the resulting granulomatous inflammation and fibrosis takes place in the liver and intestines. The magnitude of disease varies greatly from individual to individual but in a minority of patients, there is severe disease and death. S. mansoni infection in a murine model similarly results in marked strain variation of immunopathology...
2019: Frontiers in Immunology
Jing-Hua Pan, Hong Zhou, Laura Cooper, Jin-Lian Huang, Sheng-Bin Zhu, Xiao-Xu Zhao, Hui Ding, Yun-Long Pan, Lijun Rong
Background: Layilin (LAYN) is a critical gene that regulates T cell function. However, the correlations of LAYN to prognosis and tumor-infiltrating lymphocytes in different cancers remain unclear. Methods: LAYN expression was analyzed via the Oncomine database and Tumor Immune Estimation Resource (TIMER) site. We evaluated the influence of LAYN on clinical prognosis using Kaplan-Meier plotter, the PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). The correlations between LAYN and cancer immune infiltrates was investigated via TIMER...
2019: Frontiers in Immunology
Lei Tu, Lijing Yang
As a cytokine in interleukin-1(IL-1) family, interleukin-33(IL-33) usually exists in the cytoplasm and cell nucleus. When the cells are activated or damaged, IL-33 can be secreted into extracellular and regulate the functions of various immune cells through binding to its specific receptor suppression of tumorigenicity 2 (ST2). Except regulating the function of immune cells including T cells, B cells, dendritic cells (DCs), macrophages, mast cells, and innate lymphoid cells, IL-33 also plays an important role in metabolic diseases and has received an increasing attention...
2019: Frontiers in Endocrinology
Sindhu Vangeti, Jens Gertow, Meng Yu, Sang Liu, Faezzah Baharom, Saskia Scholz, Danielle Friberg, Magnus Starkhammar, Alexander Ahlberg, Anna Smed-Sörensen
Influenza A virus (IAV) infection constitutes an annual health burden across the globe. Plasmacytoid dendritic cells (PDCs) are central in antiviral defense because of their superior capacity to produce type I IFNs in response to viruses. Dendritic cells (DCs) differ depending on their anatomical location. However, only limited host-pathogen data are available from the initial site of infection in humans. In this study, we investigated how human tonsil PDCs, likely exposed to virus because of their location, responded to IAV infection compared with peripheral blood PDCs...
February 13, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
S Barillet, E Fattal, S Mura, N Tsapis, M Pallardy, H Hillaireau, S Kerdine-Römer
Modified nanoparticles (NPs) can interact with the immune system by causing its activation to fight tumors or for vaccination. During this activation, dendritic cells (DCs) are effective in generating robust immune response. However, the effect of nanomaterials on dendritic cell (DC) maturation, and the associated adjuvant effect, should be assessed as a novel biocompatibility criteria for biomaterials since immune consequences may constitute potential complications in nanomedicine. Among emerging biomaterials, poly(lactic-co-glycolic acid) NPs (PLGA NPs) are widely explored for various applications in which the degree of desired adjuvant effect may vary...
February 14, 2019: Nanotoxicology
Sonia Simonetti, Amairelys B Barroeta Seijas, Ambra Natalini, Sara Vitale, Daniele Runci, Alessandra Soriani, Antonio Di Virgilio, Eleonora Aricò, Lucia Gabriele, Angela Santoni, Francesca Di Rosa
Dendritic cells (DCs) are key players in immunity and tolerance. Some DCs express c-kit, the receptor for Stem Cell Factor (SCF), nevertheless c-kit functional role and the regulation of its expression in DCs are incompletely defined. We recently demonstrated that autocrine SCF sustains a pro-survival circuit, and that SCF increases phospho-AKT in c-kit+ mouse Bone Marrow-derived DCs (BMdDCs). Herein we observed that CpG and PolyI:C, two stimuli mimicking bacterial and viral nucleic acids respectively, strongly inhibited c-kit expression by BMdDCs and spleen DCs in vitro and in vivo...
February 13, 2019: European Journal of Immunology
Bruno Deltreggia Benites, Adriana da Silva Santos Duarte, Ana Leda Figueiredo Longhini, Irene Santos, Marisa Claudia Alvarez, Ligia Nunes de Morais Ribeiro, Eneida de Paula, Sara Teresinha Olalla Saad
Exosomes may represent an interesting antigenic pulse for new forms of anti-tumor immunotherapy. We evaluated exosomes from serum of patients with acute myeloid leukemia (AML) as an antigenic source for dendritic cells (DC) and the effects upon antitumor cytotoxicity, assessed by the percentage of specific lysis of K562 leukemic cells in co-cultures. Surprisingly, incubation of exosomes with DCs decreased lysis of K562, which may correspond to a mechanism of tumor evasion in vivo. However, when immature DCs were pulsed with exosomes purified from K562 culture supernatants, the lysis of target cells was notably enhanced, associated with a substantial increase in the expression of the maturation marker CD83...
February 9, 2019: Vaccine
Hisako Kayama, Haruka Tani, Shoko Kitada, Anunya Opasawatchai, Ryu Okumura, Daisuke Motooka, Shota Nakamura, Kiyoshi Takeda
Inappropriate activation of the interleukin (IL)-23 signaling pathway causes chronic inflammation through the induction of immunopathological Th17 cells in several tissues including the intestine, whereas adequate Th17 responses are essential for host defense against harmful organisms. In the intestinal lamina propria, IL-23 is primarily produced by innate myeloid cells including dendritic cells (DCs) and macrophages (Ms). However, the molecular mechanisms underlying the regulation of IL-23 production by these cells remains poorly understood...
February 12, 2019: International Immunology
Kee Woong Kwon, Hong-Hee Choi, Seung Jung Han, Jong-Seok Kim, Woo Sik Kim, Hongmin Kim, Lee-Han Kim, Soon Myung Kang, Jaehun Park, Sung Jae Shin
Bacillus Calmette-Guerin vaccine confers insufficient pulmonary protection against tuberculosis (TB), particularly the Mycobacterium tuberculosis (Mtb) Beijing strain infection. Identification of vaccine antigens (Ags) by considering Mtb genetic diversity is crucial for the development of improved TB vaccine. MTBK_20640, a new Beijing genotype-specific proline-glutamic acid-family Ag, was identified by comparative genomic analysis. Its immunologic features were characterized by evaluating interactions with dendritic cells (DCs), and immunogenicity and vaccine efficacy were determined against highly virulent Mtb Beijing outbreak Korean Beijing (K) strain and HN878 strain in murine infection model...
February 12, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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