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Dendritic cell immunotherapy

Pengxiang Yang, Huijuan Song, Yibo Qin, Pingsheng Huang, Chuangnian Zhang, Deling Kong, Weiwei Wang
Dendritic cells (DCs) are increasingly used in cancer vaccines due to their ability to regulate T-cell immunity. Major limitations associated with the present DCs adoptive transfer immunotherapy are low cell viability and transient duration of transplanted DCs at the vaccination site, and the lack of recruitment of host DCs, leading to unsatisfactory T-cell immune response. Here, we developed a novel vaccine nodule comprising a simple physical mixture of the peptide nanofibrous hydrogel, DCs and tumor antigens...
June 22, 2018: Nano Letters
Mona S Abdellateif, Sabry M Shaarawy, Eman Z Kandeel, Ahmed H El-Habashy, Mohamed L Salem, Motawa E El-Houseini
Dendritic cells (DCs) have been used in a number of clinical trials for cancer immunotherapy; however, they have achieved limited success in solid tumors. Consequently the aim of the present study was to identify a novel potential immunotherapeutic target for breast cancer patients through in vitro optimization of a viable DC-based vaccine. Immature DCs were primed by viable MCF-7 breast cancer cells and the activity and maturation of DCs were assessed through measuring CD83, CD86 and major histocompatibility complex (MHC)-II expression, in addition to different T cell subpopulations, namely CD4+ T cells, CD8+ T cells, and CD4+ CD25+ forkhead box protein 3 (Foxp3)+ regulatory T cells (Tregs), by flow cytometric analysis...
July 2018: Oncology Letters
Muna Alemi Yahya, Shilhav Meisel Sharon, Shay Hantisteanu, Mordechai Hallak, Ilan Bruchim
Treatment of patients with gynecologic malignancies diagnosed at advanced stages remains a therapeutic challenge. Survival rates of these patients remain significantly low, despite surgery and chemotherapy. Advances in understanding the role of the immune system in the pathogenesis of cancer have led to the rapid evolution of immunotherapeutic approaches. Immunotherapeutic strategies, including targeting specific immune checkpoints, as well as dendritic cell (DC) immunotherapy are being investigated in several malignancies, including gynecological cancers...
2018: Frontiers in Endocrinology
Heng Dong, Zhi-Fa Wen, Lin Chen, Na Zhou, Hui Liu, Shiling Dong, Hong-Ming Hu, Yongbin Mou
Background: The aim of this study was to explore the feasibility of delivering tumor antigens and enhancing the antigen cross-presentation of dendritic cells (DCs) by aluminum hydroxide nanoparticle with polyethyleneimine (PEI) modification (LV@HPA/PEI). Materials and methods: The LV@HPA nanoparticles were modified by PEI first, then the influence of LV@HPA/PEI on DCs was examined. The distinct expression of ovalbumin (OVA) protein transported into DCs by LV@HPA/PEI was observed by flow cytometry and Western blot...
2018: International Journal of Nanomedicine
Yu-Lin Su, Shuvomoy Banerjee, Seok Voon White, Marcin Kortylewski
Myeloid immune cells, such as dendritic cells, monocytes, and macrophages, play a central role in the generation of immune responses and thus are often either disabled or even hijacked by tumors. These new tolerogenic activities of tumor-associated myeloid cells are controlled by an oncogenic transcription factor, signal transducer and activator of transcription 3 (STAT3). STAT3 multitasks to ensure tumors escape immune detection by impairing antigen presentation and reducing production of immunostimulatory molecules while augmenting the release of tolerogenic mediators, thereby reducing innate and adaptive antitumor immunity...
June 19, 2018: International Journal of Molecular Sciences
Fokhrul Hossain, Samarpan Majumder, Deniz A Ucar, Paulo C Rodriguez, Todd E Golde, Lisa M Minter, Barbara A Osborne, Lucio Miele
Cancer immunotherapy, which stimulates or augments host immune responses to treat malignancies, is the latest development in the rapidly advancing field of cancer immunology. The basic principles of immunotherapies are either to enhance the functions of specific components of the immune system or to neutralize immune-suppressive signals produced by cancer cells or tumor microenvironment cells. When successful, these approaches translate into long-term survival for patients. However, durable responses are only seen in a subset of patients and so far, only in some cancer types...
2018: Frontiers in Immunology
Shin-Ichiro Fujii, Satoru Yamasaki, Yusuke Sato, Kanako Shimizu
Vaccines against a variety of infectious diseases have been developed and tested. Although there have been some notable successes, most are less than optimal or have failed outright. There has been discussion about whether either B cells or dendritic cells (DCs) could be useful for the development of antimicrobial vaccines with the production of high titers of antibodies. Invariant (i)NKT cells have direct antimicrobial effects as well as adjuvant activity, and iNKT-stimulated antigen-presenting cells (APCs) can determine the form of the ensuing humoral and cellular immune responses...
2018: Frontiers in Immunology
Kelly D Moynihan, Rebecca L Holden, Naveen K Mehta, Chensu Wang, Mark R Karver, Jens Dinter, Simon Liang, Wuhbet Abraham, Mariane B Melo, Angela Q Zhang, Na Li, Sylvie Le Gall, Bradley Pentelute, Darrell J Irvine
Antitumor T-cell responses have the potential to be curative in cancer patients, but the induction of potent T-cell immunity through vaccination remains a largely unmet goal of immunotherapy. We previously reported that the immunogenicity of peptide vaccines could be increased by maximizing delivery to lymph nodes (LNs), where T-cell responses are generated. This was achieved by conjugating the peptide to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG (DSPE-PEG) to promote albumin binding, which resulted in enhanced lymphatic drainage and improved T-cell responses...
June 18, 2018: Cancer Immunology Research
Zhijuan Qiu, Camille Khairallah, Brian S Sheridan
Listeria monocytogenes ( Lm ) infection induces robust CD8 T cell responses, which play a critical role in resolving Lm during primary infection and provide protective immunity to re-infections. Comprehensive studies have been conducted to delineate the CD8 T cell response after Lm infection. In this review, the generation of the CD8 T cell response to Lm infection will be discussed. The role of dendritic cell subsets in acquiring and presenting Lm antigens to CD8 T cells and the events that occur during T cell priming and activation will be addressed...
June 16, 2018: Pathogens
Nannan Han, Zun Zhang, Houyu Jv, Jingzhou Hu, Min Ruan, Chenping Zhang
OBJECTIVES: The aim of the present study was to investigate whether tumor-derived supernatants down-regulate the immune function of plasmacytoid dendritic cells (pDCs) in oral cancer and the potential molecular mechanisms of this effect. MATERIALS AND METHODS: Immunohistochemistry (IHC) and flow cytometry were used to detect tumor-infiltrating and peripheral blood pDCs. MTS and flow cytometry were employed to evaluate the immune response of CD4+ T cells. Real-time PCR and ELISA assays were used to identify TLR-7 and TLR-9 expression, IFN-α production and tumor-secreted soluble cytokines...
June 5, 2018: Archives of Oral Biology
Chia-Ing Jan, Wan-Chen Tsai, Horng-Jyh Harn, Woei-Cherng Shyu, Ming-Chao Liu, Hsin-Man Lu, Shao-Chih Chiu, Der-Yang Cho
Background: Glioblastoma (GBM) is the most common and lethal primary malignant glioma in adults. Dendritic cell (DC) vaccines have demonstrated promising results in GBM clinical trials. However, some patients do not respond well to DC therapy, with survival rates similar to those of conventional therapy. We retrospectively analyzed clinical and laboratory data to evaluate the factors affecting vaccine treatment. Methods: Forty-seven patients with de novo GBM were enrolled at China Medical University Hospital between 2005 and 2010 and divided into two subgroups...
2018: Frontiers in Immunology
Johannes Nowatzky, Olivier Manches, Shaukat Ali Khan, Emmanuelle Godefroy, Nina Bhardwaj
OBJECTIVE: Apoptotic cell receptors contribute to the induction of tolerance by modulating dendritic cell function following the uptake of apoptotic cells or microparticles. Dendritic cells that have bound or ingested apoptotic cells produce only low amounts of pro-inflammatory cytokines and fail to prime effector T cell responses. Specifically, ligation of the apoptotic cell receptor CR3 (CD11 b/CD18) on human monocyte-derived dendritic cells (moDC) down-modates proinflammatory cytokine secretion, but the consequences for human Th17 cell homeostasis and effector responses remain unknown...
June 13, 2018: Journal of Autoimmunity
Julie M Diamond, Claire Vanpouille-Box, Sheila Spada, Nils-Petter Rudqvist, Jessica Chapman, Beatrix Ueberheide, Karsten A Pilones, Yasmeen Sarfraz, Silvia C Formenti, Sandra Demaria
Radiotherapy (RT) used at immunogenic doses leads to accumulation of cytosolic double-stranded DNA (dsDNA) in cancer cells, which activates type I IFN (IFN-I) via the cGAS/STING pathway. Cancer cell-derived IFN-I is required to recruit BATF3-dependent dendritic cells (DCs) to poorly immunogenic tumors and trigger antitumor T-cell responses in combination with immune checkpoint blockade. We have previously demonstrated that the exonuclease TREX1 regulates radiation immunogenicity by degrading cytosolic dsDNA...
June 15, 2018: Cancer Immunology Research
N Dobrovolskienė, V Pašukonienė, A Darinskas, J A Kraśko, K Žilionytė, A Mlynska, Ž Gudlevičienė, E Mišeikytė-Kaubrienė, V Schijns, W Lubitz, P Kudela, M Strioga
Cancer immunotherapy with dendritic cell (DC)-based vaccines has been used to treat various malignancies for more than two decades, however generally showed a limited clinical success. Among various factors responsible for their modest clinical activity is the lack of universally applied, standardized protocols for the generation of clinical-grade DC vaccines, capable of inducing effective anti-tumor immune responses. We investigated Bacterial Ghosts (BGs) - empty envelopes of Gram-negative bacteria - as a tool for optimized production of DC vaccines...
June 9, 2018: Vaccine
Marinelli Oliviero, Nabissi Massimo, Morelli Maria Beatrice, Torquati Luciana, Amantini Consuelo, Santoni Giorgio
BACKGROUND: The co-stimulatory B7 family members are cell-surface protein ligands, binding to receptors on lymphocytes to regulate immune responses. One of them is the inducible co-stimulatory molecule ligand (ICOS-L). This protein is expressed on professional antigen-presenting cells (APCs), including B cells, macrophages, and dendritic cells (DCs), but it can also be expressed by endothelial cells, lung epithelium and in tumour microenvironment cells. ICOS-L is important for memory and effector T cells during the specific humoral immune responses, but its role in cancer is not yet understood...
June 7, 2018: Current Protein & Peptide Science
Chul Won Choi, Min Ho Jeong, You-Soo Park, Cheol-Hun Son, Hong-Rae Lee, Eun-Kyoung Koh
Purpose: The purpose of this study was to investigate the efficacy of stereotactic body radiation therapy (SBRT) as a tumor-associated antigen (TAA) presentation method for dendritic cell (DC) sensitization and evaluate its effect in combination with immunotherapy using an intratumoral injection of immature DCs (iDCs). Methods and Materials: CT-26 colon carcinoma cell was used as a cancer cell line. Annexin V staining and phagocytosis assays were performed to determine the appropriate radiation dose and incubation time to generate TAAs...
June 6, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Carlos R Figueiredo, Ricardo A Azevedo, Sasha Mousdell, Pedro T Resende-Lara, Lucy Ireland, Almudena Santos, Natalia Girola, Rodrigo L O R Cunha, Michael C Schmid, Luciano Polonelli, Luiz R Travassos, Ainhoa Mielgo
Mounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. While immunotherapies have shown a remarkable success in melanoma treatment, patients develop resistance by mechanisms that include the establishment of an immune suppressive tumor microenvironment. Thus, understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease...
2018: Frontiers in Immunology
Yoji Murata, Yasuyuki Saito, Takenori Kotani, Takashi Matozaki
Tumor cells evade immune surveillance through direct or indirect interactions with various types of immune cell, with much recent attention having focused on modifying immune cell responses as the basis for the development of new cancer treatments. Signal regulatory protein α (SIRPα) and CD47 are both transmembrane proteins that interact with each other and constitute a cell-cell communication system. SIRPα is particularly abundant in myeloid cells such as macrophages and dendritic cells, whereas CD47 is expressed ubiquitously and its expression level is elevated in cancer cells...
June 6, 2018: Cancer Science
Brendan J O'Sullivan, Suman Yekollu, Roland Ruscher, Ahmed M Mehdi, Muralidhara Rao Maradana, Ann P Chidgey, Ranjeny Thomas
Polymorphisms impacting thymic function may decrease peripheral tolerance and hasten autoimmune disease. The NF-κB transcription factor subunit, RelB, is essential for the development and differentiation of medullary thymic epithelial cells (mTECs): RelB-deficient mice have reduced thymic cellularity and markedly fewer mTECs, lacking AIRE. The precise mechanism of this mTEC reduction in the absence of RelB is unclear. To address this, we studied mTECs and dendritic cells (DCs), which critically regulate negative selection, and thymic regulatory T-cells (tTreg) in RelB-/- mice, which have spontaneous multiorgan autoimmune disease...
2018: Frontiers in Immunology
Lingling Zhang, Jianhua Yu, Wei Wei
Graft-versus-host disease (GVHD) is a serious and deadly complication of patients, who undergo hematopoietic stem cell transplantation (HSCT). Despite prophylactic treatment with immunosuppressive agents, 20-80% of recipients develop acute GVHD after HSCT. And the incidence rates of chronic GVHD range from 6 to 80%. Standard therapeutic strategies are still lacking, although considerable advances have been gained in knowing of the predisposing factors, pathology, and diagnosis of GVHD. Targeting immune cells, such as regulatory T cells, as well as tolerogenic dendritic cells or mesenchymal stromal cells (MSCs) display considerable benefit in the relief of GVHD through the deletion of alloactivated T cells...
2018: Frontiers in Immunology
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