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https://www.readbyqxmd.com/read/28100962/ctls-2016-and-the-formation-of-a-pan-european-professional-society-through-the-lens-of-an-abrf-founding-member
#1
Ronald L Niece
No abstract text is available yet for this article.
January 5, 2017: Journal of Biomolecular Techniques: JBT
https://www.readbyqxmd.com/read/28100832/reporter-gene-imaging-of-targeted-t-cell-immunotherapy-in-recurrent-glioma
#2
Khun Visith Keu, Timothy H Witney, Shahriar Yaghoubi, Jarrett Rosenberg, Anita Kurien, Rachel Magnusson, John Williams, Frezghi Habte, Jamie R Wagner, Stephen Forman, Christine Brown, Martin Allen-Auerbach, Johannes Czernin, Winson Tang, Michael C Jensen, Behnam Badie, Sanjiv S Gambhir
High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8(+) cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[(18)F]fluoro-3-(hydroxymethyl)butyl]guanine ([(18)F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs...
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28099147/ctla-4-positive-breast-cancer-cells-suppress-dendritic-cells-maturation-and-function
#3
Xi Chen, Qianqian Shao, Shengnan Hao, Zhonghua Zhao, Yang Wang, Xiaofan Guo, Ying He, Wenjuan Gao, Haiting Mao
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a potent immunoregulatory molecule, can down-regulate T-cell activation and inhibit anti-tumor immune response. This study showed that LPS-stimulated human dendritic cells (DCs) decreased the expression of HLA-DR, CD83 and costimulatory molecules (CD40, CD80 and CD86) following coculturing with CTLA-4+ breast cancer cells. Moreover, the suppressed DCs further inhibited proliferation of allogeneic CD4+/CD8+ T-cells, differentiation of Th1 and function of cytotoxic lymphocytes (CTLs)...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28096382/mitochondrial-activation-chemicals-synergize-with-surface-receptor-pd-1-blockade-for-t-cell-dependent-antitumor-activity
#4
Kenji Chamoto, Partha S Chowdhury, Alok Kumar, Kazuhiro Sonomura, Fumihiko Matsuda, Sidonia Fagarasan, Tasuku Honjo
Although immunotherapy by PD-1 blockade has dramatically improved the survival rate of cancer patients, further improvement in efficacy is required to reduce the fraction of less sensitive patients. In mouse models of PD-1 blockade therapy, we found that tumor-reactive cytotoxic T lymphocytes (CTLs) in draining lymph nodes (DLNs) carry increased mitochondrial mass and more reactive oxygen species (ROS). We show that ROS generation by ROS precursors or indirectly by mitochondrial uncouplers synergized the tumoricidal activity of PD-1 blockade by expansion of effector/memory CTLs in DLNs and within the tumor...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096300/enhanced-suppression-of-polyclonal-cd8-25-regulatory-t-cells-via-exosomal-arming-of-antigen-specific-peptide-mhc-complexes
#5
Chuanyong Mu, Xueshu Zhang, Lu Wang, Aizhang Xu, Khawaja Ashfaque Ahmed, Xueqin Pang, Rajni Chibbar, Andrew Freywald, Jianan Huang, Yehan Zhu, Jim Xiang
Compared with CD4(+)25(+) regulatory T cells (Tregs), the mechanisms for natural, polyclonal CD8(+)25(+) Treg immune suppression have been significantly less studied. We previously showed that polyclonal T cells can acquire antigen-specific targeting activity through arming with exosomal peptide-MHC (pMHC). In this study, we assessed the suppressive effect of CD8(+)25(+) Tregs or CD8(+)25(+) Tregs armed with ovalbumin (OVA)-specific exosomes on other immune cells and OVA-specific dendritic cell (DCOVA)-stimulated antitumor immunity...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28077684/targeting-aurora-kinase-a-and-jak2-prevents-gvhd-while-maintaining-treg-and-antitumor-ctl-function
#6
Brian C Betts, Anandharaman Veerapathran, Joseph Pidala, Hua Yang, Pedro Horna, Kelly Walton, Christopher L Cubitt, Steven Gunawan, Harshani R Lawrence, Nicholas J Lawrence, Said M Sebti, Claudio Anasetti
Graft-versus-host disease (GVHD) is a leading cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation. T cell costimulation by CD28 contributes to GVHD, but prevention is incomplete when targeting CD28, downstream mammalian target of rapamycin (mTOR), or Aurora A. Likewise, interleukin-6 (IL-6)-mediated Janus kinase 2 (JAK2) signaling promotes alloreactivity, yet JAK2 inhibition does not eliminate GVHD. We provide evidence that blocking Aurora A and JAK2 in human T cells is synergistic in vitro, prevents xenogeneic GVHD, and maintains antitumor responses by cytotoxic T lymphocytes (CTLs)...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28077213/inhibition-of-dopamine-receptor-d3-signaling-in-dendritic-cells-increases-antigen-cross-presentation-to-cd8-t-cells-favoring-anti-tumor-immunity
#7
Claudio Figueroa, Felipe Gálvez-Cancino, Cesar Oyarce, Francisco Contreras, Carolina Prado, Catalina Valeria, Sebastián Cruz, Alvaro Lladser, Rodrigo Pacheco
Dendritic cells (DCs) display the unique ability for cross-presenting antigens to CD8(+) T-cells, promoting their differentiation into cytotoxic T-lymphocytes (CTLs), which play a pivotal role in anti-tumor immunity. Emerging evidence points to dopamine receptor D3 (D3R) as a key regulator of immunity. Accordingly, we studied how D3R regulates DCs function in anti-tumor immunity. The results show that D3R-deficiency in DCs enhanced expansion of CTLs in vivo and induced stronger anti-tumor immunity. Co-culture experiments indicated that D3R-inhibition in DCs potentiated antigen cross-presentation and CTLs activation...
January 2, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28057521/biodegradable-nanoparticle-delivery-of-inactivated-swine-influenza-virus-vaccine-provides-heterologous-cell-mediated-immune-response-in-pigs
#8
Santosh Dhakal, Jagadish Hiremath, Kathryn Bondra, Yashavanth S Lakshmanappa, Duan-Liang Shyu, Kang Ouyang, Kyung-Il Kang, Basavaraj Binjawadagi, Jonathan Goodman, Kairat Tabynov, Steven Krakowka, Balaji Narasimhan, Chang-Won Lee, Gourapura J Renukaradhya
Swine influenza virus (SwIV) is one of the important zoonotic pathogens. Current flu vaccines have failed to provide cross-protection against evolving viruses in the field. Poly lactic-co-glycolic acid (PLGA) is a biodegradable FDA approved polymer and widely used in drug and vaccine delivery. In this study, inactivated SwIV H1N2 antigens (KAg) encapsulated in PLGA nanoparticles (PLGA-KAg) were prepared, which were spherical in shape with 200 to 300nm diameter, and induced maturation of antigen presenting cells in vitro...
January 2, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28056887/therapeutic-vaccine-targeting-epstein-barr-virus-latent-protein-lmp1-suppresses-lmp1-expressing-tumor-growth-and-metastasis-in-vivo
#9
Mei-Chun Lin, Yong-Chong Lin, Syue-Ting Chen, Tai-Horng Young, Pei-Jen Lou
BACKGROUND: In endemic area, nasopharyngeal carcinoma (NPC) tumor cells harbor EBV latent infection and expresses viral antigens such as EBNA1, LMP1 and LMP2. In this study, we established a NPC-mimicry animal model and assessed the therapeutic potential of LMP1 vaccine. METHODS: Animal models were established by injection of LMP1-expressing TC-1 cells in C57BL6/J mice subcutaneously or through tail veins. pcDNA3.1 empty vector or LMP1/pcDNA3.1 vaccine was delivered by a helium-driven gene gun...
January 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28024156/designer-vaccine-nanodiscs-for-personalized-cancer-immunotherapy
#10
Rui Kuai, Lukasz J Ochyl, Keith S Bahjat, Anna Schwendeman, James J Moon
Despite the tremendous potential of peptide-based cancer vaccines, their efficacy has been limited in humans. Recent innovations in tumour exome sequencing have signalled the new era of personalized immunotherapy with patient-specific neoantigens, but a general methodology for stimulating strong CD8α(+) cytotoxic T-lymphocyte (CTL) responses remains lacking. Here we demonstrate that high-density lipoprotein-mimicking nanodiscs coupled with antigen (Ag) peptides and adjuvants can markedly improve Ag/adjuvant co-delivery to lymphoid organs and sustain Ag presentation on dendritic cells...
December 26, 2016: Nature Materials
https://www.readbyqxmd.com/read/28018351/allorecognition-of-hla-c-mismatches-by-cd8-t-cells-in-hematopoietic-stem-cell-transplantation-is-a-complex-interplay-between-mismatched-peptide-binding-region-residues-hla-c-expression-and-hla-dpb1-disparities
#11
Florence Bettens, Stéphane Buhler, Jean-Marie Tiercy
HLA-C locus mismatches (MMs) are the most frequent class I disparities in unrelated hematopoietic stem cell transplantation (HSCT) and have a detrimental impact on clinical outcome. Recently, a few retrospective clinical studies have reported some variability in the immunogenicity of HLA-C incompatibilities. To get better insight into presumably permissive HLA-C MMs, we have developed a one-way in vitro mixed lymphocyte reaction (MLR) assay allowing to quantify activated CD56(-)CD137(+)CD8(+) lymphocytes in HLA-C incompatible combinations...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28011995/delivery-of-foreign-cytotoxic-t-lymphocyte-epitopes-to-tumor-tissues-for-effective-antitumor-immunotherapy-against-pre-established-solid-tumors-in-mice
#12
Herbert W Kavunja, Shuyao Lang, Suttipun Sungsuwan, Zhaojun Yin, Xuefei Huang
Cytotoxic T lymphocyte (CTL) can have remarkable abilities to kill tumor cells. However, the establishment of successful CTL-based anticancer therapy has met with many challenges. Within tumor cells, there exist subpopulations with low or no expression of the targeted antigen (termed as antigen-loss variants). In addition, tumor cells can downregulate the levels of major histocompatibility complex class I (MHC-I) molecules on cell surface due to immune pressure. As a result, some tumor cells can escape the immune pressure bestowed by CTLs, resulting in treatment failure...
December 23, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28011931/htlv-1-tax-specific-ctl-epitope-pulsed-dendritic-cell-therapy-reduces-proviral-load-in-infected-rats-with-immune-tolerance-against-tax
#13
Satomi Ando, Atsuhiko Hasegawa, Yuji Murakami, Na Zeng, Natsuko Takatsuka, Yasuhiro Maeda, Takao Masuda, Youko Suehiro, Mari Kannagi
Adult T cell leukemia/lymphoma (ATL), a CD4(+) T cell malignancy with a poor prognosis, is caused by human T cell leukemia virus type 1 (HTLV-1) infection. High proviral load (PVL) is a risk factor for the progression to ATL. We previously reported that some asymptomatic carriers had severely reduced functions of CTLs against HTLV-1 Tax, the major target Ag. Furthermore, the CTL responses tended to be inversely correlated with PVL, suggesting that weak HTLV-1-specific CTL responses may be involved in the elevation of PVL...
December 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28011817/a-mechanism-for-evasion-of-ctl-immunity-by-altered-o-glycosylation-of-hla-class-i
#14
Mihoko Sutoh Yoneyama, Yuki Tobisawa, Shingo Hatakeyama, Misaki Sato, Kiyoshi Tone, Yota Tatara, Ikuko Kakizaki, Tomihisa Funyu, Minoru Fukuda, Senji Hoshi, Chikara Ohyama, Shigeru Tsuboi
Anti-tumor immunity by cytotoxic T-lymphocytes (CTLs) is essential to suppress tumor progression. Cancer cells that evade CTL immunity proliferate in the host, promoting metastasis, but mechanisms underlying this capacity remain unknown. Here we report that bladder cancer cells metastasized to lymph nodes evade CTL immunity by a new mechanism via altered glycosylation. CTLs normally recognize and kill cancer cells presenting antigenic peptides on human leukocyte antigen (HLA) class I. We show bladder cancer cells expressing the O-glycan processing enzyme, core2 β-1,6-N-acetylglucosaminyltransferase (C2GnT) exhibit HLA class I O-glycan modified with poly-N-acetyllactosamine and are highly susceptible to CTL...
December 22, 2016: Journal of Biochemistry
https://www.readbyqxmd.com/read/28008905/the-tumour-microenvironment-harbours-ontogenically-distinct-dendritic-cell-populations-with-opposing-effects-on-tumour-immunity
#15
Damya Laoui, Jiri Keirsse, Yannick Morias, Eva Van Overmeire, Xenia Geeraerts, Yvon Elkrim, Mate Kiss, Evangelia Bolli, Qods Lahmar, Dorine Sichien, Jens Serneels, Charlotte L Scott, Louis Boon, Patrick De Baetselier, Massimiliano Mazzone, Martin Guilliams, Jo A Van Ginderachter
Various steady state and inflamed tissues have been shown to contain a heterogeneous DC population consisting of developmentally distinct subsets, including cDC1s, cDC2s and monocyte-derived DCs, displaying differential functional specializations. The identification of functionally distinct tumour-associated DC (TADC) subpopulations could prove essential for the understanding of basic TADC biology and for envisaging targeted immunotherapies. We demonstrate that multiple mouse tumours as well as human tumours harbour ontogenically discrete TADC subsets...
December 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/28003967/immune-oppression-array-elucidating-immune-escape-and-survival-mechanisms-in-uveal-melanoma
#16
Fang Hou, Qi-Ming Huang, Dan-Ning Hu, Jost B Jonas, Wen-Bin Wei
AIM: To examine the genetic profile of primary uveal melanoma (UM) as compared to UM in immune escape. METHODS: Dendritic cells (DC) loaded with lysates of UM cells of high metastatic potential were used to stimulate CTLs(CTLs). When CTLs co-cultured with the UM cells, most UM cells could be eliminated. Survival UM cells grew slowly and were considered to be survival variants and examined by a microarray analysis. These differential genes were analyzed further with Venn Diagrams and functions related to immune escape...
2016: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/27999992/c-type-lectins-their-network-and-roles-in-pathogen-recognition-and-immunity
#17
REVIEW
Sabine Mayer, Marie-Kristin Raulf, Bernd Lepenies
C-type lectins (CTLs) represent the most complex family of animal/human lectins that comprises 17 different groups. During evolution, CTLs have developed by diversification to cover a broad range of glycan ligands. However, ligand binding by CTLs is not necessarily restricted to glycans as some CTLs also bind to proteins, lipids, inorganic molecules, or ice crystals. CTLs share a common fold that harbors a Ca(2+) for contact to the sugar and about 18 invariant residues in a phylogenetically conserved pattern...
December 20, 2016: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/27999176/diacylglycerol-kinase-%C3%AE-limits-the-polarized-recruitment-of-diacylglycerol-enriched-organelles-to-the-immune-synapse-in-t-cells
#18
Elena Andrada, María Almena, Julia Sáez de Guinoa, Sara V Merino-Cortes, Rosa Liébana, Raquel Arcos, Silvia Carrasco, Yolanda R Carrasco, Isabel Merida
The antigen-induced formation of an immune synapse (IS) between T cells and antigen-presenting cells results in the rapid generation of the lipid second messenger diacylglycerol (DAG) in T cells. Diacylglycerol kinase ζ (DGKζ) converts DAG into phosphatidic acid (PA). Cytotoxic T lymphocytes (CTLs) from mice deficient in DGKζ have enhanced antiviral and antitumor activities, indicating that the amount of DAG controls the effectiveness of the T cell response. We characterized the second C1 domain of protein kinase Cθ (PKCθ), a DAG-binding protein that is specifically recruited to the IS, as a biological sensor to observe the generation of a DAG gradient during IS formation...
December 20, 2016: Science Signaling
https://www.readbyqxmd.com/read/27998971/a-phase-i-ii-study-of-cancer-peptide-vaccine-s-288310-in-patients-with-advanced-urothelial-carcinoma-of-the-bladder
#19
W Obara, M Eto, H Mimata, K Kohri, N Mitsuhata, I Miura, T Shuin, T Miki, T Koie, H Fujimoto, K Minami, Y Enomoto, T Nasu, T Yoshida, H Fuse, I Hara, K Kawaguchi, A Arimura, T Fujioka
BACKGROUND: S-288310, a cancer peptide vaccine composed of two HLA-A*24:02-restricted peptides derived from two oncoantigens, DEP domain-containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1), was investigated in urothelial carcinoma (UC) of the bladder. PATIENTS AND METHODS: Thirty eight HLA-A*24:02-positive patients with progressive UC were enrolled in this study. In the phase I part of the study, three patients each were treated with S-288310 at 1 mg or 2 mg/peptide subcutaneously once a week to evaluate safety and tolerability...
December 20, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27997610/effective-respiratory-cd8-t-cell-immunity-to-influenza-virus-induced-by-intranasal-carbomer-lecithin-adjuvanted-non-replicating-vaccines
#20
David J Gasper, Brandon Neldner, Erin H Plisch, Hani Rustom, Emily Carrow, Hirotaka Imai, Yoshihiro Kawaoka, M Suresh
CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of generating CTL responses. Adjuplex is a carbomer-lecithin-based adjuvant demonstrated to elicit robust humoral immunity to non-replicating antigens. We report that mice immunized with non-replicating Adjuplex-adjuvanted vaccines generated robust antigen-specific CTL responses...
December 2016: PLoS Pathogens
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