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https://www.readbyqxmd.com/read/28528219/the-ongoing-saga-of-the-mechanism-s-of-mhc-class-i-restricted-cross-presentation
#1
Jeff E Grotzke, Debrup Sengupta, Qiao Lu, Peter Cresswell
Cross-presentation is an MHC-I antigen processing pathway that results in the presentation of peptides from exogenous viral, bacterial, parasitic, and tumor antigens and ultimately leads to priming of naïve CD8(+) T cells. This process involves several cellular compartments and multiple components. Successful generation of MHC-I-peptide complexes requires that these components act together in a coordinated fashion. We discuss recent findings on the source of MHC-I, the role of the TAP transporter, the importance of intracellular trafficking events, mechanisms of antigen access the cytosol, and how innate immune signals can affect presentation, with an emphasis on how these pathways compare to conventional antigen presentation and how they correlate with existing data...
May 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28527686/local-innate-responses-and-protective-immunity-after-intradermal-immunization-with-bovine-viral-diarrhea-virus-e2-protein-formulated-with-a-combination-adjuvant-in-cattle
#2
Sams M A Sadat, Marlene Snider, Ravendra Garg, Robert Brownlie, Sylvia van Drunen Littel-van den Hurk
Bovine viral diarrhea virus (BVDV) is one of the most serious pathogens in cattle. Recently, we developed a novel adjuvant platform (TriAdj) that includes a toll-like receptor 3 agonist, poly (I:C); an innate defense regulatory peptide; and water-soluble polymer, poly[di(sodiumcarboxylatoethylphenoxy)]-phosphazene (PCEP). To develop a needle-free intradermal (ID) subunit vaccine, the BVDV type-2 E2 protein was formulated with TriAdj, and immune protection was evaluated in calves against a BVDV-2 strain. Intradermal delivery of E2/TriAdj elicited robust virus neutralizing antibodies and cell-mediated immune responses including CD4(+) and CD8(+) T-cell responses...
May 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28526759/il-2-high-tissue-resident-t-cells-in-the-human-liver-sentinels-for-hepatotropic-infection
#3
Laura J Pallett, Jessica Davies, Emily J Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J W Easom, Alice R Burton, Kerstin A Stegmann, Anna Schurich, Leo Swadling, Upkar S Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R Davidson, Patrick T F Kennedy, Mala K Maini
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+))...
May 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28525888/combination-of-desi2-and-ip10-gene-therapy-significantly-improves-therapeutic-efficacy-against-murine-carcinoma
#4
Chao Lin, HuaYing Yan, Jun Yang, Lei Li, Mei Tang, Xinyu Zhao, Chunlai Nie, Na Luo, Yuquan Wei, Zhu Yuan
DESI2 (also known as PNAS-4) is a novel pro-apoptotic gene activated during the early response to DNA damage. We previously reported that overexpression of DESI2 induces S phase arrest and apoptosis by activating checkpoint kinases. The present study was designed to test whether combination of DESI2 and IP10 could improve the therapy efficacy in vitro and in vivo. The recombinant plasmid co-expressing DESI2 and IP10 was encapsulated with DOTAP/Cholesterol nanoparticle. Immunocompetent mice bearing CT26 colon carcinoma and LL2 lung cancer were treated with the complex...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525366/mesenchymal-stem-cell-carriers-enhance-antitumor-efficacy-of-oncolytic-adenoviruses-in-an-immunocompetent-mouse-model
#5
Esther Rincón, Teresa Cejalvo, Deepak Kanojia, Arantzazu Alfranca, Miguel Ángel Rodríguez-Milla, Raul Andrés Gil Hoyos, Yu Han, Lingjiao Zhang, Ramón Alemany, Maciej S Lesniak, Javier García-Castro
Oncolytic virotherapy represents a promising alternative for cancer treatment; however, viral delivery to the tumor represents a major challenge. Mesenchymal stem cells (MSCs) chemotax to tumors, and can serve as a viral delivery tool. Previously, we demonstrated antitumor therapeutic efficacy for mesenchymal stem cells (MSCs) infected with the oncolytic human adenovirus ICOVIR5 (Celyvir) for treatment of neuroblastoma patients. Given the lack of suitable immunocompetent preclinical models, the mechanism underlying Celyvir antitumor activity remains unknown...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523113/human-serum-albumin-delivered-au-pet3-is-a-potent-inhibitor-of-t-cell-proliferation
#6
Tyler C Dean, Mu Yang, Mingyong Liu, Jason M Grayson, Anthony W DeMartino, Cynthia S Day, Jingyun Lee, Cristina M Furdui, Ulrich Bierbach
Using a modular library format in conjunction with cell viability (MTS) and flow cytometry assays, 90 cationic complexes [AuPL] (n+) (P = phosphine ligand; L = thiourea derivative or chloride) were studied for their antiproliferative activity in CD8(+) T lymphocyte cells. The activity of the compounds correlates with the steric bulk of the phosphine ligands. Thiourea serves as a leaving group that is readily replaced by cysteine thiol (NMR, ESI-MS). Taking advantage of selective thiourea ligand exchange, the fragments [Au(PEt3)](+) and [Au(JohnPhos)](+) (JohnPhos = 1,1'-biphenyl-2-yl)di-tert-butylphosphine) in compounds 1 and 2 were transferred to recombinant human serum albumin (rHSA)...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28523003/hpv16-e7-specific-activated-cd8-t-cells-in-e7-transgenic-skin-and-skin-grafts
#7
Seyed Davoud Jazayeri, Paula T Kuo, Graham Robert Leggatt, Ian H Frazer
Human papillomavirus (HPV) 16 E7 (E7) protein expression in skin promotes epithelial hyperproliferation and transformation to malignancy. Grafts of murine skin expressing E7 protein as a transgene in keratinocytes are not rejected from immunocompetent recipients, whereas grafts expressing ovalbumin (OVA), with or without coexpression of E7 protein, are promptly rejected, demonstrating that E7-associated non-antigen-specific local immunosuppression is not a major determinant of lack of rejection of E7 transgenic skin...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28522749/expansion-of-tumor-infiltrating-cd8-t-cells-expressing-pd-1-improves-the-efficacy-of-adoptive-t-cell-therapy
#8
Sarita M Fernandez-Poma, Diego Salas-Benito, Teresa Lozano, Noelia Casares, José-Ignacio Riezu-Boj, Uxua Mancheño, Edurne Elizalde, Diego Alignani, Natalia Zubeldia, Itziar Otano, Enrique Conde, Pablo Sarobe, Juan J Lasarte, Sandra Hervas-Stubbs
Recent studies have found that tumor-infiltrating lymphocytes (TIL) expressing PD-1 can recognize autologous tumor cells, suggesting that cells derived from PD-1+ TIL can be used in adoptive T cell therapy (ACT). However, no study thus far has evaluated the antitumor activity of PD-1-selected TIL in vivo. In two mouse models of solid tumors, we show that PD-1 allows identification and isolation of tumor-specific TIL without previous knowledge of their antigen specificities. Importantly, despite the high proportion of tumor-reactive T cells present in bulk CD8 TIL before expansion, only T cell products derived from sorted PD-1+, but not from PD-1- or bulk CD8 TIL, specifically recognized tumor cells...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28522585/herpes-simplex-virus-glycoprotein-d-targets-a-specific-dendritic-cell-subset-and-improves-the-performance-of-vaccines-to-human-papillomavirus-associated-tumors
#9
Bruna F M M Porchia, Ana Carolina R Moreno, Rodrigo N Ramos, Mariana O Diniz, Laís Helena T M de Andrade, Daniela S Rosa, José Alexandre M Barbuto, Silvia B Boscardin, Luís Carlos S Ferreira
Cervical cancer is a major public health problem and one of the leading causes of cancer deaths in women. Virtually all cases of cervical cancer, as well as a growing share of anal and head/neck tumors, are associated with human papillomavirus (HPV) infection. Despite the effectiveness, the available prophylactic vaccines do not benefit women with cervical lesions or cancer. Therefore, the search of new immunotherapeutic approaches to treat HPV-induced tumors is still a priority. The present study characterizes a therapeutic antitumor vaccine based on the genetic fusion of the Herpes simplex virus-1 (HSV-1) glycoprotein D (gD) with the E7 oncoprotein from HPV-16 (gDE7)...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522454/multiomic-disease-signatures-converge-to-cytotoxic-cd8-t-cells-in-primary-sj%C3%A3-gren-s-syndrome
#10
Shinya Tasaki, Katsuya Suzuki, Ayumi Nishikawa, Yoshiaki Kassai, Maiko Takiguchi, Rina Kurisu, Yuumi Okuzono, Takahiro Miyazaki, Masaru Takeshita, Keiko Yoshimoto, Hidekata Yasuoka, Kunihiro Yamaoka, Kazuhiro Ikeura, Kazuyuki Tsunoda, Rimpei Morita, Akihiko Yoshimura, Hiroyoshi Toyoshiba, Tsutomu Takeuchi
OBJECTIVES: Multiomics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren's syndrome (SS) pathology. METHODS: We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. RESULTS: Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins...
May 18, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28521477/t-cell-immunity-induced-by-a-bivalent-salmonella-based-ceacam6-and-4-1bbl-vaccines-in-a-rat-colorectal-cancer-model
#11
Chunhui Jin, Xiaoqing Duan, Yingying Liu, Jianhong Zhu, Ke Zhang, Yuanting Zhang, Tingting Xia, Yajun Fei, Jianxin Ye
The present study investigated the anti-tumor mechanisms of recombinant non-specific cross-reacting antigen (CEACAM6) and 4-1BB ligand (4-1BBL) Salmonella-based vaccines, and the effect that these vaccinations have on memory T cells and T helper (Th) cell polarization. Colon tumors were induced in rats via 1,2-dimethylhydrazine (DMH) injections. Rats were then treated with injections of attenuated Salmonella typhimurium carrying pIRES-CEACAM6, pIRES-4-1BBL or pIRES-CEACAM6-4-1BBL. In total, 4 vaccine injections, one every other week, were administered during the 8 weeks subsequent to the DMH injection...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521429/b-cells-inhibit-the-antitumor-immunity-against-an-established-murine-fibrosarcoma
#12
Andrea Maglioco, Damián G Machuca, María Noel Badano, Paula Nannini, Gabriela V Camerano, Héctor Costa, Roberto Meiss, Raúl A Ruggiero, Mirta Giordano, Graciela I Dran
Despite the classic role of B cells in favoring the immune response, an inhibitory action of B lymphocytes in tumor immunity has emerged in certain studies. In methylcolanthrene-induced murine fibrosarcoma (MCC), the loss of immunogenicity and the establishment of tolerance are paralleled by systemic immune suppression and the appearance of B(+)IL-10(+) cells in tumor-draining lymph nodes. The present study aimed to assess the role of the B(+)IL-10(+) cell population in the immune evasion and tolerance induced by MCC through the depletion of B cells in mice at various times of tumor progression: Prior to or subsequent to tumor implantation...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521292/tumor-infiltrating-immune-cells-and-prognosis-in-gastric-cancer-a-systematic-review-and-meta-analysis
#13
Wen Jiang, Ke Liu, Qing Guo, Ji Cheng, Liming Shen, Yinghao Cao, Jing Wu, Jianguo Shi, Heng Cao, Bo Liu, Kaixiong Tao, Guobin Wang, Kailin Cai
Tumor-infiltrating immune cells are a pivotal component of the tumor microenvironment (TME), but their indicative role remains poorly defined. A meta-analysis was performed to reveal the prognostic efficiency of tumor-infiltrating immune cells in gastric cancer (GC). By searching PubMed and Embase, we identified a total of 35 eligible articles that involved 4888 patients. Random or fixed effect models were employed to extract pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Our results indicated that high CD3+ lymphocyte infiltration in all the locations (AG), the tumor nest (TN), and the tumor stroma (TS) predicted better overall survival (OS) (HR=0...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28520183/infected-malnourished-children-displayed-changes-in-early-activation-and-lymphocyte-subpopulations
#14
Oralia Nájera-Medina, Fernando Valencia-Chavarría, Consuelo Cortés-Bejar, Monika Palacios-Martínez, C Paulina Rodríguez-López, María Cristina González-Torres
AIM: Malnutrition and infections cause immunological changes in lymphocyte subpopulations and their functionality. We evaluated the activation capacity of lymphocytes and memory cells in 10 well nourished, seven well nourished infected and eight malnourished infected children before and after treatment. METHODS: All the children were patients in Mexico City and were less than three years of age. The expression of various cluster of differentiation (CD) cells were assessed by flow cytometry: CD45RA (naïve) and CD45RO (memory) antigens on CD4 lymphocytes and CD69 in all lymphocytes...
May 18, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/28518161/erratum-epigenetic-landscapes-reveal-transcription-factors-that-regulate-cd8-t-cell-differentiation
#15
Bingfei Yu, Kai Zhang, J Justin Milner, Clara Toma, Runqiang Chen, James P Scott-Browne, Renata M Pereira, Shane Crotty, John T Chang, Matthew E Pipkin, Wei Wang, Ananda W Goldrath
No abstract text is available yet for this article.
May 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28515724/an-analysis-of-trafficking-receptors-shows-that-cd44-and-p-selectin-glycoprotein-ligand-1-collectively-control-the-migration-of-activated-human-t-cells
#16
Amal J Ali, Ayman F Abuelela, Jasmeen S Merzaban
Selectins guide the traffic of activated T-cells through the blood stream by mediating their tethering and rolling onto inflamed endothelium, in this way acting as beacons to help navigate them to sites of inflammation. Here, we present a comprehensive analysis of E-selectin ligands expressed on activated human T-cells. We identified several novel glycoproteins that function as E-selectin ligands. Specifically, we compared the role of P-selectin glycoprotein ligand-1 (PSGL-1) and CD43, known E-selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28515360/a-human-psmb11-variant-affects-thymoproteasome-processing-and-cd8-t-cell-production
#17
Izumi Ohigashi, Yuki Ohte, Kazuya Setoh, Hiroshi Nakase, Akiko Maekawa, Hiroshi Kiyonari, Yoko Hamazaki, Miho Sekai, Tetsuo Sudo, Yasuharu Tabara, Hiromi Sawai, Yosuke Omae, Rika Yuliwulandari, Yasuhito Tanaka, Masashi Mizokami, Hiroshi Inoue, Masanori Kasahara, Nagahiro Minato, Katsushi Tokunaga, Keiji Tanaka, Fumihiko Matsuda, Shigeo Murata, Yousuke Takahama
The Psmb11-encoded β5t subunit of the thymoproteasome, which is specifically expressed in cortical thymic epithelial cells (cTECs), is essential for the optimal positive selection of functionally competent CD8+ T cells in mice. Here, we report that a human genomic PSMB11 variation, which is detectable at an appreciable allele frequency in human populations, alters the β5t amino acid sequence that affects the processing of catalytically active β5t proteins. The introduction of this variation in the mouse genome revealed that the heterozygotes showed reduced β5t expression in cTECs and the homozygotes further exhibited reduction in the cellularity of CD8+ T cells...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28515356/licensing-delineates-helper-and-effector-nk-cell-subsets-during-viral-infection
#18
Anthony E Zamora, Ethan G Aguilar, Can M Sungur, Lam T Khuat, Cordelia Dunai, G Raymond Lochhead, Juan Du, Claire Pomeroy, Bruce R Blazar, Dan L Longo, Jeffrey M Venstrom, Nicole Baumgarth, William J Murphy
Natural killer (NK) cells can be divided into phenotypic subsets based on expression of receptors that bind self-MHC-I molecules, a concept termed licensing or education. Here we show NK cell subsets with different migratory, effector, and immunoregulatory functions in dendritic cell and antigen (ag)-specific CD8+ T cell responses during influenza and murine cytomegalovirus infections. Shortly after infection, unlicensed NK cells localized in draining lymph nodes and produced GM-CSF, which correlated with the expansion and activation of dendritic cells, and resulted in greater and sustained ag-specific T cell responses...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28515346/the-novel-complex-combination-of-alum-cpg-odn-and-hh2-as-adjuvant-in-cancer-vaccine-effectively-suppresses-tumor-growth-in-vivo
#19
Yaomei Tian, Meng Li, Chaoheng Yu, Rui Zhang, Xueyan Zhang, Rong Huang, Lian Lu, Fengjiao Yuan, Yingzi Fan, Bailing Zhou, Ke Men, Heng Xu, Li Yang
Single-component adjuvant is prone to eliciting a specific type of Th1 or Th2 response. So, the development of combinatorial adjuvants inducing a robust mixed Th1/Th2 response is a promising vaccination strategy against cancer. Here, we describe a novel combination of aluminum salts (alum), CpG oligodeoxynucleotide (CpG) and innate defense regulator peptide HH2 for improving anti-tumor immune responses. The CpG-HH2 complex significantly enhanced the production of IFN-γ, TNF-α and IL-1β, promoted the uptake of antigen and strengthened the activation of p38, Erk1/2 and NF-κB in vitro, compared to CpG or HH2 alone...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515303/spontaneous-and-vaccine-induced-clearance-of-mus-musculus-papillomavirus-type-1-mmupv1-muspv1-infection
#20
Rosie T Jiang, Joshua W Wang, Shiwen Peng, Tsui-Chin Huang, Chenguang Wang, Fabiana Cannella, Yung-Nien Chang, Raphael P Viscidi, Simon R A Best, Chien-Fu Hung, Richard B S Roden
Mus musculus Papillomavirus1 (MmuPV1/MusPV1) induces persistent papillomas in immunodeficient mice but not common laboratory strains. To facilitate study of immune control, we sought an outbred and immune competent laboratory mouse strain in which persistent papillomas could be established. We found that challenge of SKH1 mice (Crl:SKH1-Hrhr) by scarification on their tail with MmuPV1 resulted in three clinical outcomes: 1) persistent (>2 months) papillomas (∼20%), 2) transient papillomas that spontaneously regress typically within 2 months (∼15%), 3) no visible papillomas and viral clearance (∼65%)...
May 17, 2017: Journal of Virology
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