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Dendritic tumor

Evgenii Tcyganov, Jerome Mastio, Eric Chen, Dmitry I Gabrilovich
In recent years, myeloid-derived suppressor cells (MDSC) have emerged as one of the major inhibitors of immune effector cell function in cancer. MDSC represent a heterogeneous population of largely immature myeloid cells that are characterized by a pathological state of activation and display potent immune suppressive activity. Two major subsets of MDSC have been identified: monocytic (M-MDSC) and polymorphonuclear (PMN-MDSC). PMN-MSDC share phenotypic and morphologic features with neutrophils, whereas M-MDSC are similar to monocytes and are characterized by high plasticity...
March 13, 2018: Current Opinion in Immunology
Clémence Granier, Alain Gey, Charles Dariane, Arnaud Mejean, Marc-Olivier Timsit, Charlotte Blanc, Virginie Verkarre, Camélia Radulescu, Elisabeth Fabre, Yann Vano, Stéphane Oudard, Cécile Badoual, Éric Tartour
T cells harboring multiple co-inhibitory molecules lose their anti-tumoral functionality. PD-1 is a clinically approved target in cancer therapy, but its expression alone does not mean dysfunctionality. The expression of Tim-3 on numerous cell types (T cell, Treg, dendritic cell, myeloid cells) favors tumor escape to immune cells. Within many tumors, PD-1/Tim-3 coexpressing CD8-T cells lose their ability to secrete cytokines (IFNγ, IL-2, TNFα) and their intratumoral infiltration correlates with a bad prognosis...
March 2018: Médecine Sciences: M/S
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...
March 14, 2018: Melanoma Research
Emilia Vendelova, Diyaaeldin Ashour, Patrick Blank, Florian Erhard, Antoine-Emmanuel Saliba, Ulrich Kalinke, Manfred B Lutz
Dendritic cells (DCs) are key directors of tolerogenic and immunogenic immune responses. During the steady state, DCs maintain T cell tolerance to self-antigens by multiple mechanisms including inducing anergy, deletion, and Treg activity. All of these mechanisms help to prevent autoimmune diseases or other hyperreactivities. Different DC subsets contribute to pathogen recognition by expression of different subsets of pattern recognition receptors, including Toll-like receptors or C-type lectins. In addition to the triggering of immune responses in infected hosts, most pathogens have evolved mechanisms for evasion of targeted responses...
2018: Frontiers in Immunology
Felix S Lichtenegger, Maurine Rothe, Frauke M Schnorfeil, Katrin Deiser, Christina Krupka, Christian Augsberger, Miriam Schlüter, Julia Neitz, Marion Subklewe
Immune checkpoint inhibition has been shown to successfully reactivate endogenous T cell responses directed against tumor-associated antigens, resulting in significantly prolonged overall survival in patients with various tumor entities. For malignancies with low endogenous immune responses, this approach has not shown a clear clinical benefit so far. Therapeutic vaccination, particularly dendritic cell (DC) vaccination, is a strategy to induce T cell responses. Interaction of DCs and T cells is dependent on receptor-ligand interactions of various immune checkpoints...
2018: Frontiers in Immunology
Brittany P Lassiter, Siqi Guo, Stephen J Beebe
Nano-pulse stimulation (NPS), previously called nsPEFs, induced a vaccine-like effect after ablation of orthotopic N1-S1 hepatocellular carcinoma (HCC), protecting rats from subsequent challenges with N1-S1 cells. To determine immunity, immune cell phenotypes were analyzed in naïve, treated and protected rats. NPS provides a positive, post-ablation immuno-therapeutic outcome by alleviating immunosuppressive T regulatory cells (Treg) in the tumor microenvironment (TME), allowing dendritic cell influx and inducing dynamic changes in natural killer cells (NKs), NKT-cells and T-lymphocytes in blood, spleen and liver...
March 13, 2018: Cancers
Tsukasa Seya, Yohei Takeda, Ken Takashima, Sumito Yoshida, Masahiro Azuma, Misako Matsumoto
The immune system eliminates advanced cancer when treated with programmed cell death protein-1 (PD-1) or its ligand (PD-L1) blockade, but PD-1 therapy is effective in only ∼20% of patients with solid cancer. The PD-1 antibody mainly acts on the effector phase of cytotoxic T lymphocytes (CTLs) in tumors but induces no activation of the priming phase of antigen-presenting dendritic cells (DCs). It is reasonable that both DC-priming and PD-1/L1 blocking are mandatory for efficient CTL-mediated tumor cytolysis...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
Pei Zhang, Xuguang Hu, Bin Liu, Zhe Liu, Cong Liu, Jianming Cai, Fu Gao, Jianguo Cui, Bailong Li, Yanyong Yang
BACKGROUND Carbon ion radiotherapy has been shown to be more effective in cancer radiotherapy than photon irradiation. Influence of carbon ion radiation on cancer microenvironment is very important for the outcomes of radiotherapy. Tumor-infiltrating dendritic cells (DCs) play critical roles in cancer antigen processing and antitumor immunity. However, there is scant literature covering the effects of carbon ion radiation on DCs. In this study, we aimed to uncover the impact of carbon ion irradiation on bone marrow derived DCs...
March 11, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Weihua Hou, Ping Wei, Jianlan Xie, Yuanyuan Zheng, Yanlin Zhang, Xiaoge Zhou
This study concerning mantle cell lymphoma (MCL) investigated retrospectively an association between patient prognosis and the percentage of the total number of lymphoma cells found in the follicular dendritic cell (FDC) meshwork, that is, the degree of overlap of lymphoma cells. Two hundred and nine MCL patients were apportioned to grades I-III, in which the CD21-positive FDC meshwork covered ≤50%, 51%-89%, and ≥90% of the tumor area, respectively. Significant differences among the grades (all, P < 0...
February 21, 2018: Pathology, Research and Practice
Mariana Terra, Marine Oberkampf, Catherine Fayolle, Pierre Rosenbaum, Camille Guillerey, Gilles Dadaglio, Claude Leclerc
A growing number of observations has suggested that plasmacytoid dendritic cells (pDC) play a critical role in tumor biology. In patients, infiltration of tumors by pDC generally correlates with a poor prognosis, suggesting that pDC may play an important role in the host-tumor relationship. Here we analyze the influence of pDC in solid tumor development using two different tumor models: TC-1 and B16-OVA. Phenotypic and functional gene profiling analysis of tumor-associated pDC showed that the tumor microenvironment affected their activation status and ability to produce cytokines and chemokines...
March 9, 2018: Cancer Research
Alessia Gallo, Monica Miele, Ester Badami, Pier Giulio Conaldi
Patients following solid organ transplantation show a higher risk of developing cancer compared to the general population. Elevated risk is likely due to the interplay of a combination of factors, such as chronic inflammation, coexisting medical conditions, immunosuppressive regimen and persistent infection with oncogenic viruses. In addition, the tumor microenvironment plays a pivotal role in cancer progression, by driving recruitment and in situ differentiation of anti-inflammatory cells of the adaptive and innate immune system such as regulatory T cells, Th17, Dendritic Cells, Myeloid Derived Suppressor Cells, Type 2 Macrophages...
February 16, 2018: Cellular Immunology
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)...
March 8, 2018: Melanoma Research
Luka Brcic, Stefanie Stanzer, Dagmar Krenbek, Ulrike Gruber-Moesenbacher, Gudrun Absenger, Franz Quehenberger, Arschang Valipour, Joerg Lindenmann, Herbert Stoeger, Mohamed Al Effah, Melanie Fediuk, Marija Balic, Helmut H Popper
Squamous cell and adenocarcinomas of the lung develop different mechanisms during carcinogenesis to evade attacks of the immune system. Besides the well-known check-point control programmed death 1 and its ligand, many more mechanisms, acting either tumoricidal or in favor of tumor progression, exist. Analysis of the immune cell profiles in resected tissues and bronchoalveolar lavage samples and correlation between them and with overall survival data was performed. In all tumor samples in this study, cells of the immune system expressed a tumor-cooperating phenotype...
March 8, 2018: Virchows Archiv: An International Journal of Pathology
Shinya Yamamoto, Kazuhiko Matsuo, Daisuke Nagakubo, Shintaro Higashiyama, Keiji Nishiwaki, Naoki Oiso, Akira Kawada, Osamu Yoshie, Takashi Nakayama
CCR4 is a major chemokine receptor expressed by Treg cells that downregulate immune responses. Here, we investigated the role of CCR4-mediated Treg cell recruitment in antigen-specific immune responses. CCR4-deficient mice immunized intramuscularly with ovalbumin (OVA) showed enhanced OVA-specific IgG responses. Furthermore, intramuscular administration of OVA induced the expression of MDC/CCL22, a ligand for CCR4, in macrophages of the muscle tissues, and enhanced the recruitment of CCR4+ Treg cells in wild-type mice, whereas this recruitment of Treg cells was severely impaired in CCR4-deficient mice...
February 8, 2018: Journal of Pharmacological Sciences
Hatem Soliman, Fatema Khambati, Hyo S Han, Roohi Ismail-Khan, Marilyn M Bui, Daniel M Sullivan, Scott Antonia
Background: Indoleamine 2, 3-dioxygenase is an enzyme that causes immunosuppression in tumors. Indoximod inhibits the indoleamine 2, 3-dioxygenase pathway and enhances immunologic responses to dendritic cell (DC) vaccines preclinically. Adenovirus p53 (Ad.p53) is used to generate DC vaccines against p53. A phase-1/2 trial of indoximod with Ad.p53-DC vaccine was conducted. Materials and Methods: The phase-1 study combined 7 indoximod dose levels with < 6 Ad.p53-DC vaccinations every 2 weeks...
February 9, 2018: Oncotarget
Tridib Das, Zhongli Chen, Rudi W Hendriks, Mirjam Kool
Immune cell activation is a stringently regulated process, as exaggerated innate and adaptive immune responses can lead to autoinflammatory and autoimmune diseases. Perhaps the best-characterized molecular pathway promoting cell activation is the nuclear factor-κB (NF-κB) signaling pathway. Stimulation of this pathway leads to transcription of numerous pro-inflammatory and cell-survival genes. Several mechanisms tightly control NF-κB activity, including the key regulatory zinc finger (de)ubiquitinating enzyme A20/tumor necrosis factor α-induced protein 3 (TNFAIP3)...
2018: Frontiers in Immunology
Hsiang-I Tsai, Lijuan Jiang, Xiaowei Zeng, Hongbo Chen, Zihuang Li, Wei Cheng, Jinxie Zhang, Jie Pan, Dong Wan, Li Gao, Zhenhua Xie, Laiqiang Huang, Lin Mei, Gan Liu
The clinical applications of platinum-based antitumor agents are still largely limited by severe side effects as well as multidrug resistance (MDR). To solve these problems, we developed an 1,2-diaminocyclohexane-platinum(II) (DACHPt)-loaded nanoparticle (NP-TPGS-Pt) by self-assembly of poly(amidoamine)-polyglutamic acid- b -D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PGlu- b -TPGS) and DACHPt. NP-TPGS-Pt showed robust stability and pH-responsive DACHPt release profile in vitro similar to the PEG-containing nanoparticle (NP-PEG-Pt)...
2018: Frontiers in Pharmacology
Sarah L Buchan, Mohannah Fallatah, Stephen M Thirdborough, Vadim Y Taraban, Anne Rogel, Lawrence J Thomas, Christine A Penfold, Li-Zhen He, Michael A Curran, Tibor Keler, Aymen Al-Shamkhani
PURPOSE: PD-1 checkpoint blockade has revolutionized the field of cancer immunotherapy, yet the frequency of responding patients is limited by inadequate T-cell priming secondary to a paucity of activatory dendritic cells (DCs). DC signals can be bypassed by CD27 agonists and we therefore investigated if the effectiveness of anti-PD-1/L1 could be improved by combining with agonist anti-CD27 monoclonal antibodies (mAb). EXPERIMENTAL DESIGN: The efficacy of PD-1/L1 blockade or agonist anti-CD27 mAb was compared with a dual-therapy approach in multiple tumor models...
March 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Jing Xie, Demao Zhang, Yunfeng Lin, Quan Yuan, Xuedong Zhou
BACKGROUND: The meniscus plays an important role in knee joint diseases such as osteoarthritis (OA). Meniscal injuries can be accompanied by joint catabolic events initiated by inflammation, leading to articular cartilage destruction, but the cellular events responsible for intrinsic meniscal injury and the extracellular matrix changes necessary for meniscal degradation are not well known. PURPOSE: To explore the cellular and matrix-related changes of menisci based on a mouse OA model of anterior cruciate ligament transection (ACLT)...
March 1, 2018: American Journal of Sports Medicine
Najmeh Khosravianfar, Jamshid Hadjati, Afshin Namdar, Roobina Boghozian, Morteza Hafezi, Mahboubeh Ashourpour, Nasim Kheshtchin, Mahsa Banitalebi, Reza Mirzaei, Seyed Alireza Razavi
Myeloid-derived suppressor cells (MDSCs) are capable of suppressing the immune response. 5-Fluorouracil (5-FU) compared to other chemotherapy drugs have shown considerable decreases in the number of MDSCs without visible effects on T, B and natural killer cells, as well as dendritic cells (DCs). DC-based vaccines considered to be appropriate candidates for cancer immunotherapy. However, due to the presence of various factors like MDSCs in tumor microenvironment, DC vaccine cannot effectively perform its function...
February 2018: Iranian Journal of Allergy, Asthma, and Immunology
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