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https://www.readbyqxmd.com/read/29046894/fatty-acid-mimetic-micelles-for-dual-delivery-of-antigens-and-imidazoquinoline-adjuvants
#1
Sema Sevimli, Frances C Knight, Pavlo Gilchuk, Sebastian Joyce, John T Wilson
Vaccine design has undergone a shift towards the use of purified protein subunit vaccines, which offer increased safety and greater control over antigen specificity, but at the expense of immunogenicity. Here we report the development of a new polymer-based vaccine delivery platform engineered to enhance immunity through the co-delivery of protein antigens and the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ). Owing to the preferential solubility of IMQ in fatty acids, a series of block copolymer micelles with a fatty acid-mimetic core comprising lauryl methacrylate (LMA) and methacrylic acid (MAA), and a poly(ethylene glycol) methyl ether methacrylate (PEGMA) corona decorated with pyridyl disulfide ethyl methacrylate (PDSM) moieties for antigen conjugation were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization...
February 13, 2017: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/28993771/tumor-derived-microvesicles-modulate-antigen-cross-processing-via-reactive-oxygen-species-mediated-alkalinization-of-phagosomal-compartment-in-dendritic-cells
#2
Federico Battisti, Chiara Napoletano, Hassan Rahimi Koshkaki, Francesca Belleudi, Ilaria Grazia Zizzari, Ilary Ruscito, Sara Palchetti, Filippo Bellati, Pierluigi Benedetti Panici, Maria Rosaria Torrisi, Giulio Caracciolo, Fabio Altieri, Marianna Nuti, Aurelia Rughetti
Dendritic cells (DCs) are the only antigen-presenting cells able to prime naïve T cells and cross-prime antigen-specific CD8(+) T cells. Their functionality is a requirement for the induction and maintenance of long-lasting cancer immunity. Albeit intensively investigated, the in vivo mechanisms underlying efficient antigen cross-processing and presentation are not fully understood. Several pieces of evidence indicate that antigen transfer to DCs mediated by microvesicles (MVs) enhances antigen immunogenicity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28963110/development-diversity-and-function-of-dendritic-cells-in-mouse-and-human
#3
David A Anderson, Kenneth M Murphy, Carlos G Briseño
The study of murine dendritic cell (DC) development has been integral to the identification of specialized DC subsets that have unique requirements for their form and function. Advances in the field have also provided a framework for the identification of human DC counterparts, which appear to have conserved mechanisms of development and function. Multiple transcription factors are expressed in unique combinations that direct the development of classical DCs (cDCs), which include two major subsets known as cDC1s and cDC2s, and plasmacytoid DCs (pDCs)...
September 29, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28961609/dcone-as-an-allogeneic-cell-based-vaccine-for-multiple-myeloma
#4
Rebecca Karp Leaf, Dina Stroopinsky, Athalia R Pyzer, Ada M Kruisbeek, Sandra van Wetering, Abigail Washington, Adam Ephraim, Leandra Cole, Adam Morin, Salvia Jain, Myrna R Nahas, Arik Apel, Jon Arnason, Ayad Hamdan, Jacalyn Rosenblatt, David Avigan
Multiple myeloma (MM) is characterized by progressive immune dysregulation, loss of myeloma-specific immunity, and an immunosuppressive milieu that fosters disease growth and immune escape. Accordingly, cancer vaccines that reverse tumor-associated immune suppression represent a promising therapeutic avenue of investigation. We examined the potential of an allogeneic cellular vaccine to generate immune responses against MM tumor cells. The DCOne vaccine is comprised of a human myeloid leukemia cell line differentiated into a fully functional dendritic cell, expressing a range of tumor-associated antigens that are also known targets in MM...
November 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28960134/differential-requirement-of-rab22a-for-the-recruitment-of-er-derived-proteins-to-phagosomes-and-endosomes-in-dendritic-cells
#5
Cristina Croce, Luis S Mayorga, Ignacio Cebrian
The recruitment of endoplasmic reticulum (ER) components to dendritic cell (DC) phagosomes and endosomes is a crucial event to achieve efficient cross-presentation of exogenous antigens. We have previously identified the small GTPase Rab22a as a key regulator of MHC-I trafficking and antigen cross-presentation by DCs. In this study we show that low expression of Rab22a does not prevent the normal delivery of ER-derived proteins to DC phagosomes. In contrast, the presence of these proteins was diminished in endosomes labelled with a fluid phase marker...
September 29, 2017: Small GTPases
https://www.readbyqxmd.com/read/28959385/dominant-immunosuppression-of-dendritic-cell-function-by-prostate-cancer-derived-exosomes
#6
Josephine Salimu, Jason Webber, Mark Gurney, Saly Al-Taei, Aled Clayton, Zsuzsanna Tabi
Exosomes are a distinct population of extracellular vesicles of endocytic origin with a protein repertoire similar to the parent cell. Although tumour-derived exosomes harbour immunosuppressive characteristics, they also carry tumour antigens and thus potentially contribute to immune activation. The aim of this study was to examine the impact of prostate cancer exosomes on tumour antigen cross-presentation. DU145 cells, transduced with shRNA to knockdown Rab27a (DU145(KD)) that inhibits exosome secretion, triggered significantly stronger tumour-antigen-specific T cell responses when loaded onto dendritic cells (DC) than control DU145 cells...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28959259/transmembrane-helices-are-an-overlooked-source-of-major-histocompatibility-complex-class-i-epitopes
#7
Frans Bianchi, Johannes Textor, Geert van den Bogaart
About a fourth of the human proteome is anchored by transmembrane helices (TMHs) to lipid membranes. TMHs require multiple hydrophobic residues for spanning membranes, and this shows a striking resemblance with the requirements for peptide binding to major histocompatibility complex (MHC) class I. It, therefore, comes as no surprise that bioinformatics analysis predicts an over-representation of TMHs among strong MHC class I (MHC-I) binders. Published peptide elution studies confirm that TMHs are indeed presented by MHC-I...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28947859/modulation-of-dendritic-cell-apoptosis-and-cd8-cytotoxicity-by-histamine-role-of-protein-kinase-c
#8
Julieta Alcain, Enrique Podaza, María Soledad Gori, Gabriela Salamone, Mónica Vermeulen
Dendritic cells (DC) are able to present extracellular antigens associated with the molecules of the major histocompatibility complex class I. In a previous work, we demonstrated that the histamine (HIS), acting through H1/H4 receptors, increases the cross-presentation of soluble ovalbumin by murine DC and can enhance the recruitment of specific CD8(+) T lymphocytes during the development of chronic inflammatory responses. Here, we studied in more depth the mechanisms underlying this enhancement. We showed that the cytotoxicity of specific CD8(+) lymphocytes is increased in HIS-treated DC and it is lost by inhibition of vacuolar-ATPase that prevents endosome acidification...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28945841/antigen-cross-presentation-and-t-cell-cross-priming-in-cancer-immunology-and-immunotherapy
#9
Alfonso R Sánchez-Paulete, Álvaro Teijeira, Francisco J Cueto, Saray Garasa, José L Pérez-Gracia, Álvaro Sánchez-Arráez, David Sancho, Ignacio Melero
Dendritic cells are the main professional antigen-presenting cells for induction of T cell adaptive responses. Cancer cells express tumor antigens, including neoantigens generated by non-synonymous mutations, but are poor for antigen presentation and for providing costimulatory signals for T-cell priming. Mounting evidence suggests that antigen transfer to dendritic cells (DCs) and their surrogate presentation on MHC class I and II molecules together with costimulatory signals is paramount for induction of viral and cancer immunity...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28884480/blood-monocytes-sample-melana-mart1-antigen-for-long-lasting-cross-presentation-to-cd8-t-cells-after-differentiation-into-dendritic-cells
#10
Florence Faure, Mabel Jouve, Isabelle Lebhar-Peguillet, Charlotte Sadaka, Fernando Sepulveda, Olivier Lantz, Stefano Berre, Raphael Gaudin, Silvia Sánchez-Ramón, Sebastian Amigorena
Human blood monocytes are very potent to take up antigens. Like macrophages in tissue, they efficiently degrade exogenous protein and are less efficient than dendritic cells (DCs) at cross-presenting antigens to CD8(+) T cells. Although it is generally accepted that DCs take up tissue antigens and then migrate to lymph nodes to prime T cells, the mechanisms of presentation of antigens taken up by monocytes are poorly documented so far. In the present work, we show that monocytes loaded in vitro with MelanA long peptides retain the capacity to stimulate antigen-specific CD8(+) T cell clones after 5 days of differentiation into monocytes-derived dendritic cells (MoDCs)...
September 7, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28876002/engineering-biodegradable-guanidyl-decorated-peg-pcl-nanoparticles-as-robust-exogenous-activators-of-dcs-and-antigen-cross-presentation
#11
Pan Li, Huijuan Song, Hao Zhang, Pengxiang Yang, Chuangnian Zhang, Pingsheng Huang, Deling Kong, Weiwei Wang
Nanoparticles (NPs)-based adjuvants are attracting much attention in the development of vaccines. Previously, we reported a type of guanidyl-decorated polymeric NPs used as antigen delivery carriers for the first time. However, its un-degradability may restrict potential clinical translation. More importantly, the specific cellular pathway by which dendritic cells (DCs) endocytosed these NPs and the relationship among guanidyl with the antigen cross-presentation, cytokine secretion, and lymph node targeting still remain unclear...
September 21, 2017: Nanoscale
https://www.readbyqxmd.com/read/28872140/purification-of-the-membrane-compartment-for-endoplasmic-reticulum-associated-degradation-of-exogenous-antigens-in-cross-presentation
#12
Jun Imai, Mayu Otani, Takahiro Sakai, Shinichi Hatta
Dendritic cells (DCs) are highly capable of processing and presenting internalized exogenous antigens upon major histocompatibility class (MHC) I molecules also known as cross-presentation (CP). CP plays an important role not only in the stimulation of naïve CD8(+) T cells and memory CD8(+) T cells for infectious and tumor immunity but also in the inactivation of self-acting naïve T cells by T cell anergy or T cell deletion. Although the critical molecular mechanism of CP remains to be elucidated, accumulating evidence indicates that exogenous antigens are processed through endoplasmic reticulum-associated degradation (ERAD) after export from non-classical endocytic compartments...
August 21, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28864471/peripheral-deletion-of-cd8-t-cells-requires-p38-mapk-in-cross-presenting-dendritic-cells
#13
Trevor Smith, Xiaotian Lin, Marielle Mello, Kristi Marquardt, Jocelyn Cheung, Binfeng Lu, Linda A Sherman, Grégory Verdeil
Peripheral tolerance mechanisms exist to prevent autoimmune destruction by self-reactive T cells that escape thymic deletion. Dominant tolerance imposed by CD4(+)Foxp3(+) T regulatory cells can actively control autoaggressive T cell responses. Tolerance mechanisms that act endogenous to the T cell also exist. These mechanisms include T cell inactivation (anergy) and deletion. A major difference between anergic T cells and T cells undergoing peripheral deletion is the capacity of the latter to still signal through MAPKs upon TCR stimulation, suggesting these signals may be required for T deletion...
October 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28851692/photodynamic-immune-checkpoint-therapy-eradicates-local-and-distant-tumors-by-cd8-t-cells
#14
Jan Willem Kleinovink, Marieke F Fransen, Clemens W Löwik, Ferry Ossendorp
Photodynamic therapy (PDT) is a clinically applied tumor ablation method that reduces tumor burden and may induce T-cell responses, providing a therapeutic option for mutated tumors. In this study, we applied PDT in two mouse tumor models and assessed its effect on outgrowth of PDT-treated and distant untreated tumors. PDT of established tumors resulted in complete tumor eradication in most mice, which were then protected against tumor rechallenge. Correspondingly, the therapeutic effect was abrogated upon systemic depletion of CD8(+) T cells, indicating PDT-induced tumor antigen cross-presentation and T-cell activation...
August 29, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28842467/role-of-lymphocyte-subsets-in-the-immune-response-to-primary-b-cell-derived-exosomes
#15
Sarah C Saunderson, Alexander D McLellan
Exosomes are lipid nanovesicles released after fusion of the endosomal limiting membrane with the plasma membrane. In this study, we investigated the requirement for CD4 T cells, B cells, and NK cells to provide help for CD8 T cell-mediated response to B cell-derived exosomes. CTL responses to Ag-loaded exosomes were dependent on host MHC class I, with a critical role for splenic langerin(+) CD8α(+) dendritic cells (DCs) in exosomal Ag cross-presentation. In addition, there was an absolute dependence on the presence of CD4 T cells, CD8 T cells, and NK cells, where the loss of any one of these subsets led to a complete loss of CTL response...
August 25, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28829049/the-march-family-joins-the-antigen-cross-presentation-party
#16
Justine D Mintern, José A Villadangos
No abstract text is available yet for this article.
October 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28819024/trastuzumab-increases-her2-uptake-and-cross-presentation-by-dendritic-cells
#17
Victor A Gall, Anne V Philips, Na Qiao, Karen Clise-Dwyer, Alexander A Perakis, Mao Zhang, Guy T Clifton, Pariya Sukhumalchandra, Qing Ma, Sangeetha M Reddy, Dihua Yu, Jeffrey J Molldrem, George E Peoples, Gheath Alatrash, Elizabeth A Mittendorf
Early-phase clinical trials evaluating CD8(+) T cell-eliciting, HER2-derived peptide vaccines administered to HER2(+) breast cancer patients in the adjuvant setting suggest synergy between the vaccines and trastuzumab, the mAb targeting the HER2 protein. Among 60 patients enrolled in clinical trials evaluating the E75 + GM-CSF and GP2 + GM-CSF vaccines, there have been no recurrences in patients vaccinated after receiving trastuzumab as part of standard therapy in the per treatment analyses conducted after a median follow-up of greater than 34 months...
October 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28783704/constitutive-resistance-to-viral-infection-in-human-cd141-dendritic-cells
#18
Aymeric Silvin, Chun I Yu, Xavier Lahaye, Francesco Imperatore, Jean-Baptiste Brault, Sylvain Cardinaud, Christian Becker, Wing-Hong Kwan, Cécile Conrad, Mathieu Maurin, Christel Goudot, Santy Marques-Ladeira, Yuanyuan Wang, Virginia Pascual, Esperanza Anguiano, Randy A Albrecht, Matteo Iannacone, Adolfo García-Sastre, Bruno Goud, Marc Dalod, Arnaud Moris, Miriam Merad, A Karolina Palucka, Nicolas Manel
Dendritic cells (DCs) are critical for the launching of protective T cell immunity in response to viral infection. Viruses can directly infect DCs, thereby compromising their viability and suppressing their ability to activate immune responses. How DC function is maintained in light of this paradox is not understood. By analyzing the susceptibility of primary human DC subsets to viral infections, we report that CD141(+) DCs have an innate resistance to infection by a broad range of enveloped viruses, including HIV and influenza virus...
July 7, 2017: Science Immunology
https://www.readbyqxmd.com/read/28767693/dendritic-cells-that-phagocytose-apoptotic-macrophages-loaded-with-mycobacterial-antigens-activate-cd8-t-cells-via-cross-presentation
#19
Patricia Espinosa-Cueto, Alejandro Magallanes-Puebla, Carlos Castellanos, Raul Mancilla
While homeostatic apoptosis is immunologically silent, macrophage apoptosis during Mycobacterium tuberculosis infection can potentially induce an immune response against the mycobacteria. To examine the role of dendritic cells in this response, macrophage apoptosis was induced by incubating the macrophage with cell wall extracts of mycobacteria expressing LpqH. The apoptogenic proteins of the cell wall extracts were engulfed by the macrophage and then were translocated from the cytosol to the nuclei of the dying cells...
2017: PloS One
https://www.readbyqxmd.com/read/28756740/c-type-lectin-receptor-s-targeted-nanoliposomes-an-intelligent-approach-for-effective-cancer-immunotherapy
#20
Rajeev Sharma, Nishi Mody, Varun Kushwah, Sanyog Jain, S P Vyas
AIM: The purpose of present approach is to target C-Type lectin (CTL) receptors for preferential uptake by the macrophages/dendritic cells and improving the cross-presentation of ovalbumin. MATERIALS & METHODS: Conventional and engineered nanoliposomes (MPNLs) were fabricated and extensively characterized. The nanoliposome(s) was spherical in shape; and their ζ potential, size and ovalbumin loading efficiency were recorded to be 268 ± 4.15 nm, 23.4 ± 0.35 mV, 46...
July 31, 2017: Nanomedicine
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