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"Cross presentation"

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https://www.readbyqxmd.com/read/29229919/migratory-dendritic-cells-acquire-and-present-lymphatic-endothelial-cell-archived-antigens-during-lymph-node-contraction
#1
Ross M Kedl, Robin S Lindsay, Jeffrey M Finlon, Erin D Lucas, Rachel S Friedman, Beth A Jirón Tamburini
Antigens derived from viral infection or vaccination can persist within a host for many weeks after resolution of the infection or vaccine responses. We previously identified lymphatic endothelial cells (LEC) as the repository for this antigen archival, yet LECs are unable to present their archived antigens to CD8+ T cells, and instead transfer their antigens to CD11c+ antigen-presenting cells (APC). Here we show that the exchange of archived antigens between LECs and APCs is mediated by migratory dendritic cells (DC)...
December 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29220492/hbv-derived-synthetic-long-peptide-can-boost-cd4-and-cd8-t-cell-responses-in-chronic-hbv-patients-ex-vivo
#2
Yingying Dou, Nadine van Montfoort, Aniek van den Bosch, Robert A de Man, Gijs G Zom, Willem-Jan Krebber, Cornelis J M Melief, Sonja I Buschow, Andrea M Woltman
Background: Vaccination with Synthetic Long Peptides (SLP ®) is a promising new treatment strategy for chronic HBV (CHB). SLP can induce broad T cell responses for all HLA types. Here we investigated the ability of a prototype HBV-core (HBc)-sequence-derived SLP to boost HBV-specific T cells in CHB patients ex vivo. Methods: HBc-SLP was used to assess cross-presentation by monocyte-derived DC(moDC) and BDCA1+ blood myeloid DC (mDC) to engineered HBV-specific CD8+ T cells...
December 6, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29198621/innate-immune-receptors-for-cross-presentation-the-expanding-role-of-nlrs
#3
Daniele Corridoni, Alison Simmons
A critical role of pattern recognition receptors (PRRs) is to influence adaptive immune responses by regulating antigen presentation. Engagement of PRRs in dendritic cells (DCs) increases MHC class I antigen presentation and CD8+ T-cell activation by cross-presented peptides but the molecular mechanisms underlying these effects are not completely understood. Studies looking at the role of PRRs in cross-presentation have been largely limited to TLRs but the role of other PRRs such as cytosolic nucleotide-binding oligomerization domain-like (NOD-like) receptors remains particularly enigmatic...
November 29, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29177671/creation-of-recombinant-chaperone-vaccine-using-large-heat-shock-protein-for-antigen-targeted-cancer-immunotherapy
#4
Chunqing Guo, John R Subjeck, Xiang-Yang Wang
Large heat shock proteins (HSPs) or stress proteins, including Hsp110 and Grp170, are unique molecular chaperones with superior capability of shuttling tumor protein antigens into professional antigen-presenting cells, such as dendritic cells, for highly efficient cross-presentation and T cell priming. Reconstituted chaperone complexes of large HSP and tumor protein antigen have been demonstrated to generate a robust antigen-specific T lymphocyte response with therapeutic potency against multiple cancer types in preclinical models...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29176619/stim1-promotes-migration-phagosomal-maturation-and-antigen-cross-presentation-in-dendritic-cells
#5
Paula Nunes-Hasler, Sophia Maschalidi, Carla Lippens, Cyril Castelbou, Samuel Bouvet, Daniele Guido, Flavien Bermont, Esen Y Bassoy, Nicolas Page, Doron Merkler, Stéphanie Hugues, Denis Martinvalet, Bénédicte Manoury, Nicolas Demaurex
Antigen cross-presentation by dendritic cells (DC) stimulates cytotoxic T cell activation to promote immunity to intracellular pathogens, viruses and cancer. Phagocytosed antigens generate potent T cell responses, but the signalling and trafficking pathways regulating their cross-presentation are unclear. Here, we show that ablation of the store-operated-Ca2+-entry regulator STIM1 in mouse myeloid cells impairs cross-presentation and DC migration in vivo and in vitro. Stim1 ablation reduces Ca2+ signals, cross-presentation, and chemotaxis in mouse bone-marrow-derived DCs without altering cell differentiation, maturation or phagocytic capacity...
November 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29175591/linking-t-cell-epitopes-to-a-common-linear-b-cell-epitope-a-targeting-and-adjuvant-strategy-to-improve-t-cell-responses
#6
Sara M Mangsbo, Erika A K Fletcher, Wendy W C van Maren, Anke Redeker, Robert A Cordfunke, Inken Dillmann, Jasper Dinkelaar, Kahina Ouchaou, Jeroen D C Codee, Gijs A van der Marel, Peter Hoogerhout, Cornelis J M Melief, Ferry Ossendorp, Jan W Drijfhout
Immune complexes are potent mediators of cellular immunity and have been extensively studied for their disease mediating properties in humans and for their role in anti-cancer immunity. However, a viable approach to use antibody-complexed antigen as vehicle for specific immunotherapy has not yet reached clinical use. Since virtually all people have endogenous antibodies against tetanus toxoid (TTd), such commonly occurring antibodies are promising candidates to utilize for immune modulation. As an initial proof-of-concept we investigated if anti-tetanus IgG could induce potent cross-presentation of a conjugate with SIINFEKL, a MHC class I presented epitope of ovalbumin (OVA), to TTd...
November 22, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29163786/axl-inhibition-induces-the-antitumor-immune-response-which-can-be-further-potentiated-by-pd-1-blockade-in-the-mouse-cancer-models
#7
Zhiqiang Guo, Yan Li, Dandan Zhang, Jiaying Ma
Immune checkpoint blockers (ICB) have emerged as a promising new class of antitumor agents which significantly change the treatment landscape in a range of tumors; however, cancer patients benefited from ICB-based immunotherapy remains limited, scoring the need to explore the combination treatments with synergistic mechanisms of action. Axl receptor tyrosine kinase critically involves in the carcinogenesis of multiple cancers due to its dual roles in both promoting cancer invasion and metastasis and suppressing myeloid cell activation and function...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163493/alpha-galactosylceramide-cd1d-antibody-fusion-proteins-redirect-invariant-natural-killer-t-cell-immunity-to-solid-tumors-and-promote-prolonged-therapeutic-responses
#8
REVIEW
Lianjun Zhang, Alena Donda
Major progress in cancer immunotherapies have been obtained by the use of tumor targeting strategies, in particular with the development of bi-functional fusion proteins such as ImmTacs or BiTes, which engage effector T cells for targeted elimination of tumor cells. Given the significance of invariant natural killer T (iNKT) cells in bridging innate and adaptive immunity, we have developed a bi-functional protein composed of the extracellular part of CD1d molecule that was genetically fused to an scFv fragment from high affinity antibodies against HER2 or CEA...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29158474/unc93b1-interacts-with-the-calcium-sensor-stim1-for-efficient-antigen-cross-presentation-in-dendritic-cells
#9
Sophia Maschalidi, Paula Nunes-Hasler, Clarissa R Nascimento, Ignacio Sallent, Valérie Lannoy, Meriem Garfa-Traore, Nicolas Cagnard, Fernando E Sepulveda, Pablo Vargas, Ana-Maria Lennon-Duménil, Peter van Endert, Thierry Capiod, Nicolas Demaurex, Guillaume Darrasse-Jèze, Bénédicte Manoury
Dendritic cells (DC) have the unique ability to present exogenous antigens via the major histocompatibility complex class I pathway to stimulate naive CD8(+) T cells. In DCs with a non-functional mutation in Unc93b1 (3d mutation), endosomal acidification, phagosomal maturation, antigen degradation, antigen export to the cytosol and the function of the store-operated-Ca(2+)-entry regulator STIM1 are impaired. These defects result in compromised antigen cross-presentation and anti-tumor responses in 3d-mutated mice...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29147022/conventional-cd4-t-cells-present-bacterial-antigens-to-induce-cytotoxic-and-memory-cd8-t-cell-responses
#10
Aránzazu Cruz-Adalia, Guillermo Ramirez-Santiago, Jesús Osuna-Pérez, Mónica Torres-Torresano, Virgina Zorita, Ana Martínez-Riaño, Viola Boccasavia, Aldo Borroto, Gloria Martínez Del Hoyo, José María Gozález-Granado, Balbino Alarcón, Francisco Sánchez-Madrid, Esteban Veiga
Bacterial phagocytosis and antigen cross-presentation to activate CD8+ T cells are principal functions of professional antigen presenting cells. However, conventional CD4+ T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8+ T cells, which proliferate and become cytotoxic in response. CD4+ T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8+ T cells with low PD-1 expression...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29144754/immunogenic-cell-death-amplified-by-co-localized-adjuvant-delivery-for-cancer-immunotherapy
#11
Yuchen Fan, Rui Kuai, Yao Xu, Lukasz J Ochyl, Darrell J Irvine, James J Moon
Despite their potential, conventional whole-cell cancer vaccines prepared by freeze-thawing or irradiation have shown limited therapeutic efficacy in clinical trials. Recent studies have indicated that cancer cells treated with certain chemotherapeutics, such as mitoxantrone, can undergo immunogenic cell death (ICD) and initiate antitumor immune responses. However, it remains unclear how to exploit ICD for cancer immunotherapy. Here, we present a new material-based strategy for converting immunogenically dying tumor cells into a powerful platform for cancer vaccination and demonstrate their therapeutic potential in murine models of melanoma and colon carcinoma...
November 22, 2017: Nano Letters
https://www.readbyqxmd.com/read/29142130/effective-priming-of-hsv-specific-cd8-t-cells-in-vivo-does-not-require-infected-dendritic-cells
#12
Paul G Whitney, Christina Makhlouf, Beth MacLeod, Joel Z Ma, Elise Gressier, Marie Greyer, Katharina Hochheiser, Annabell Bachem, Ali Zaid, David Voehringer, William R Heath, Mayura V Wagle, Ian Parish, Tiffany A Russell, Stewart A Smith, David C Tscharke, Thomas Gebhardt, Sammy Bedoui
Resolution of virus infections depends on the priming of virus-specific CD8(+) T cells by dendritic cells (DC). While this process requires MHC class I-restricted antigen presentation by DC, the relative contribution to CD8(+) T cell priming by infected DC is less clear. We have addressed this question in the context of a peripheral infection with herpes simplex virus type 1 (HSV). Assessing the endogenous, polyclonal HSV-specific CD8(+) T cell response, we found that effective in vivo T cell priming depended on the presence of DC subsets specialized in cross-presentation while Langerhans cells and plasmacytoid DC were dispensable...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29128232/liposome-based-immunity-inducing-systems-for-cancer-immunotherapy
#13
REVIEW
Eiji Yuba
Cancer immunotherapy has gained much attention for next-generation cancer treatment. To conduct cancer immunotherapy, efficient antigen delivery systems must be able to deliver an antigen selectively to antigen-presenting cells, release it at suitable sites for induction of cross-presentation, and simultaneously induce activation of immunocompetent cells. Liposomes are a candidate for use as such multifunctional antigen delivery carriers because of their capability for easy functionalization. This review describes the rational design of liposome-based antigen delivery systems...
November 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29126597/role-of-autophagy-in-mhc-class-i-restricted-antigen-presentation
#14
Luc Van Kaer, Vrajesh V Parekh, J Luke Postoak, Lan Wu
Major histocompatibility complex (MHC) class I molecules present peptide antigens to MHC class I-restricted CD8(+) T lymphocytes. The peptides loaded onto MHC class I molecules are typically derived from cytosolic antigens, which includes both self and foreign proteins. In addition to this classical MHC class I antigen presentation pathway, some cell types, especially dendritic cells can present antigens from exogenous sources to MHC class I-restricted CD8(+) T cells, in a process called cross-presentation...
November 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29100330/protective-cellular-immunity-generated-by-cross-presenting-recombinant-overlapping-peptide-proteins
#15
Lili Cai, Jianbo Zhang, Renying Zhu, Weixing Shi, Xiaobing Xia, Mark Edwards, William Finch, Anthony Coombs, Ju Gao, Kangwen Chen, Sophie Owen, Shisong Jiang, Wenshu Lu
Priming of naive CD8(+) and CD4(+) T cells by dendritic cells (DCs) requires effective antigen presentation on both MHC class I and II molecules. We have developed a novel technology to use recombinant overlapping peptides (ROP) that stimulate both CD8(+) and CD4(+) T cell immune responses. The single chain protein of a ROP is made up of overlapping peptides linked by the target sequence (LRMK) for cathepsin S, a protease found in the endosomes of DCs. We designed synthetic genes encoding ROPs derived from ovalbumin (OVA), tuberculosis protein (CFP10-ESAT6), human papilloma virus (HPV) protein (E7) and survivin, a protein commonly over-expressed in tumour cells...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29091760/a-discrete-subset-of-monocyte-derived-cells-among-typical-conventional-type-2-dendritic-cells-can-efficiently-cross-present
#16
Jianpeng Sheng, Qi Chen, Irene Soncin, See Liang Ng, Klaus Karjalainen, Christiane Ruedl
Dendritic cells (DCs) and macrophages (Mϕs) share close developmental pathways and functional features, leading to blurring of the boundaries between these two cell lineages. However, a deeper understanding of DC and Mϕ ontogeny and more refined phenotypic and functional characterizations have helped to delineate pre-DC-derived conventional DCs (cDCs), including cDC1s and cDC2s, from monocyte-derived Mϕs. Here, we further refine DC/Mϕ cell classification and report that classically defined cDC2s contain a discrete population of monocyte-derived migratory antigen-presenting cells with Mϕ phenotype but functional DC features, including cross-presentation...
October 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/29079107/dissecting-antigen-processing-and-presentation-routes-in-dermal-vaccination-strategies
#17
Anouk C M Platteel, Sandrine Henri, Dietmar M Zaiss, Alice J A M Sijts
The skin is an attractive site for vaccination due to its accessibility and presence of immune cells surveilling this barrier. However, knowledge of antigen processing and presentation upon dermal vaccination is sparse. In this study we determined antigen processing routes that lead to CD8(+) T cell activation following dermal DNA tattoo immunization, exploiting a model antigen that contains an immunoproteasome-dependent epitope. In agreement with earlier reports, we found that DNA tattoo immunization of wild type (WT) mice triggered vigorous responses to the immunoproteasome-dependent model epitope, whereas gene-deficient mice lacking the immunoproteasome subunits β5i/LMP7 and β2i/MECL1 failed to respond...
October 24, 2017: Vaccine
https://www.readbyqxmd.com/read/29070650/interleukin-12-from-cd103-batf3-dependent-dendritic-cells-required-for-nk-cell-suppression-of-metastasis
#18
Deepak Mittal, Dipti Vijayan, Eva M Putz, Amelia R Aguilera, Kate A Markey, Jasmin Straube, Stephen Kazakoff, Stephen L Nutt, Kazuyoshi Takeda, Geoffrey R Hill, Nicola Waddell, Mark J Smyth
Several host factors may affect the spread of cancer to distant organs, however the intrinsic role of dendritic cells (DCs) in controlling metastasis is poorly described. Here we show in several tumor models that although the growth of primary tumors in Batf3-deficient mice, which lack cross-presenting DCs, was not different from primary tumors in wild-type (WT) control mice, Batf-deficient mice had increased experimental and spontaneous metastasis and poorer survival. The increased metastasis was independent of CD4+ and CD8+ T lymphocytes, but required NK cells and IFNγ...
October 25, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29062313/dead-tumor-cells-expressing-infectious-salmon-anemia-virus-fusogenic-protein-favor-antigen-cross-priming-in-vitro
#19
Jonathan Morales, Carlos Barrera-Avalos, Carlos Castro, Stephanie Castillo, Claudio Barrientos, Claudia Robles-Planells, Ximena López, Ernesto Torres, Margarita Montoya, Marcelo Cortez-San Martín, Denise Riquelme, Alejandro Escobar, Ricardo Fernández, Mónica Imarai, Daniela Sauma, Leonel E Rojo, Elias Leiva-Salcedo, Claudio Acuña-Castillo
Antigen cross-presentation is a crucial step in the assembly of an antitumor immune response leading to activation of naïve CD8 T cells. This process has been extensively used in clinical trials, in which dendritic cells generated in vitro are loaded with tumor antigens and then autotransplanted to the patients. Recently, the use of autologous transplant of dendritic cells fused with dying tumor cells has demonstrated good results in clinical studies. In this work, we generated a similar process in vivo by treating mice with dead tumor cells [cell bodies (CBs)] expressing the fusogenic protein of the infectious salmon anemia virus (ISAV)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29051851/biomimetically-engineered-demi-bacteria-potentiate-vaccination-against-cancer
#20
Dezhi Ni, Shuang Qing, Hui Ding, Hua Yue, Di Yu, Shuang Wang, Nana Luo, Zhiguo Su, Wei Wei, Guanghui Ma
Failure in enhancing antigen immunogenicity has limited the development of cancer vaccine. Inspired by effective immune responses toward microorganisms, demi-bacteria (DB) from Bacillus are engineered as carriers for cancer vaccines. The explored hydrothermal treatment enables the Bacillus to preserve optimal pathogen morphology with intrinsic mannose receptor agonist. Meanwhile, the treated Bacillus can be further endowed with ideal hollow/porous structure for efficient accommodation of antigen and adjuvant, such as CpG...
October 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
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