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https://www.readbyqxmd.com/read/28821192/could-the-pd-1-pathway-be-a-potential-target-for-treating-small-intestinal-adenocarcinoma
#1
Ramya Thota, Raul S Gonzalez, Jordan Berlin, Dana B Cardin, Chanjuan Shi
Objectives: The programmed death 1 (PD-1) pathway is upregulated in the immune microenvironment of many cancers. In this study, we examined the PD-1 pathway and the immune microenvironment of small intestinal adenocarcinomas by immunohistochemistry. Methods: From our department pathology archives we identified 42 small intestinal adenocarcinomas from between 2000 and 2015, with blocks available for IHC studies. Tumors were immunohistochemically stained for CD3, CD4, CD8, CD20, PD-1, and programmed death ligand 1 (PD-L1) expression...
September 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28820360/preliminary-study-on-the-changes-of-ovarian-reserve-menstruation-and-lymphocyte-subpopulation-in-systemic-lupus-erythematosus-sle-patients-of-childbearing-age
#2
H Gao, J Ma, X Wang, T Lv, J Liu, Y Ren, Y Li, Y Zhang
Objective The main aim of this study was to investigate the ovarian reserve, menstruation, and lymphocyte subpopulation in systemic lupus erythematosus (SLE) patients of childbearing age. Methods We enrolled 40 SLE patients of childbearing age and 40 age-matched healthy controls. Anti-Müllerian hormone (AMH) was tested by electrochemiluminescence, and lymphocyte subsets were tested by flow cytometry. Menstruation situation was obtained by interview. Results The AMH level of the SLE group was significantly lower than that of the control group ( p < 0...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28819257/cytolytic-dna-vaccine-encoding-lytic-perforin-augments-the-maturation-of-and-antigen-presentation-by-dendritic-cells-in-a-time-dependent-manner
#3
Danushka K Wijesundara, Wenbo Yu, Ben J C Quah, Preethi Eldi, John D Hayball, Kerrilyn R Diener, Ilia Voskoboinik, Eric J Gowans, Branka Grubor-Bauk
The use of cost-effective vaccines capable of inducing robust CD8(+) T cell immunity will contribute significantly towards the elimination of persistent viral infections and cancers worldwide. We have previously reported that a cytolytic DNA vaccine encoding an immunogen and a truncated mouse perforin (PRF) protein significantly augments anti-viral T cell (including CD8(+) T cell) immunity. Thus, the current study investigated whether this vaccine enhances activation of dendritic cells (DCs) resulting in greater priming of CD8(+) T cell immunity...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819024/trastuzumab-increases-her2-uptake-and-cross-presentation-by-dendritic-cells
#4
Victor A Gall, Anne V Philips, Na Qiao, Karen Clise-Dwyer, Alexander A Perakis, Mao Zhang, Guy Travis 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-positive breast cancer patients in the adjuvant setting suggest synergy between the vaccines and trastuzumab, the monoclonal antibody targeting the HER2 protein. Among 60 patients enrolled on 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...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28819022/%C3%AE-adrenergic-signaling-in-mice-housed-at-standard-temperatures-suppresses-an-effector-phenotype-in-cd8-t-cells-and-undermines-checkpoint-inhibitor-therapy
#5
Mark J Bucsek, Guanxi Qiao, Cameron R MacDonald, Thejaswini Giridharan, Lauren Evans, Brian Niedzwecki, Haichao Liu, Kathleen M Kokolus, Jason W-L Eng, Michelle N Messmer, Kristopher Attwood, Scott I Abrams, Bonnie L Hylander, Elizabeth A Repasky
The immune context of tumors has significant prognostic value and is predictive of responsiveness to several forms of therapy, including immunotherapy. We report here that CD8(+) T cell frequency and functional orientation within the tumor microenvironment is regulated by β2-adrenergic receptor (β-AR) signaling in host immune cells. We used three strategies - physiologic (manipulation of ambient thermal environment), pharmacologic (β-blockers), and genetic (β2-adrenergic receptor knockout mice) to reduce adrenergic stress signaling in two widely studied preclinical mouse tumor models...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28818721/immunomodulatory-effects-of-herbal-formula-of-astragalus-polysaccharide-aps-and-polysaccharopeptide-psp-in-mice-with-lung-cancer
#6
Xing Zhou, Zijing Liu, Tingting Long, Lijng Zhou, Yixi Bao
OBJECTIVE: This study is to investigate the immunomodulatory effects of the herbal formula of astragalus polysaccharide (APS) and polysaccharopeptide (PSP) in mouse models of immunosuppression and lung cancer. METHODS: Immune parameters were recorded for these model mice. Peripheral white blood cells (WBC) were detected with the automatic blood cell analyzer. Spleen and thymus indices, and tumor inhibition ratio were obtained. Percentage of peripheral blood CD4(+) and CD8(+) T lymphocytes were detected by flow cytometry...
August 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28818640/the-influence-of-physical-activity-in-the-anti-tumor-immune-response-in-experimental-breast-tumor
#7
Thiago M Bianco, Douglas R Abdalla, Chamberttan S Desidério, Sofie Thys, Cindy Simoens, John-Paul Bogers, Eddie F C Murta, Márcia A Michelin
This study aimed to investigate the influence of physical activity in innate immunity to conduce to an effective antitumoral immune response analyzing the phenotype and activation status of infiltrating cells. We analyzed the intracellular cytokines and the transcription factors of tumor infiltrating lymphocytes (TILS) and spleen leukocytes. The Nos2 gene expression was evaluated in spleen cells and futhermore the ROS production was measured and spleen cells; another cell evaluated was dendritic cells (TIDCs), their cytokines expression and membrane molecules; finally to understood the results obtained, we analysed the dendritic cells obtained from bone marrow...
August 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28818060/rna-transfection-of-%C3%AE-%C3%AE-t-cells-with-a-chimeric-antigen-receptor-or-an-%C3%AE-%C3%AE-t-cell-receptor-a-safer-alternative-to-genetically-engineered-%C3%AE-%C3%AE-t-cells-for-the-immunotherapy-of-melanoma
#8
Dennis C Harrer, Bianca Simon, Shin-Ichiro Fujii, Kanako Shimizu, Ugur Uslu, Gerold Schuler, Kerstin F Gerer, Stefanie Hoyer, Jan Dörrie, Niels Schaft
BACKGROUND: Adoptive T-cell therapy relying on conventional T cells transduced with T-cell receptors (TCRs) or chimeric antigen receptors (CARs) has caused substantial tumor regression in several clinical trials. However, genetically engineered T cells have been associated with serious side-effects due to off-target toxicities and massive cytokine release. To obviate these concerns, we established a protocol adaptable to GMP to expand and transiently transfect γ/δ T cells with mRNA...
August 17, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28817839/evaluating-the-effect-of-immune-cells-on-the-outcome-of-patients-with-mesothelioma
#9
Serena J Chee, Maria Lopez, Toby Mellows, Sharmali Gankande, Karwan A Moutasim, Scott Harris, James Clarke, Pandurangan Vijayanand, Gareth J Thomas, Christian H Ottensmeier
BACKGROUND: We systematically assessed the prognostic and predictive value of infiltrating adaptive and innate immune cells in a large cohort of patients with advanced mesothelioma. METHODS: A tissue microarray from 302 samples was constructed. Markers of adaptive immune response in T-cells (CD8(+), FOXP3(+), CD4(+), CD45RO(+), CD3(+)) and B-cells (CD20(+)), and of innate immune response; neutrophils (NP57(+)), natural killer cells (CD56(+)) and macrophages (CD68(+)) were evaluated...
August 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28817635/contractile-actomyosin-arcs-promote-the-activation-of-primary-mouse-t-cells-in-a-ligand-dependent-manner
#10
Jinsung Hong, Sricharan Murugesan, Eric Betzig, John A Hammer
Mechano-transduction is an emerging but still poorly understood component of T cell activation. Here we investigated the ligand-dependent contribution made by contractile actomyosin arcs populating the peripheral supramolecular activation cluster (pSMAC) region of the immunological synapse (IS) to T cell receptor (TCR) microcluster transport and proximal signaling in primary mouse T cells. Using super resolution microscopy, OT1-CD8+ mouse T cells, and two ovalbumin (OVA) peptides with different affinities for the TCR, we show that the generation of organized actomyosin arcs depends on ligand potency and the ability of myosin 2 to contract actin filaments...
2017: PloS One
https://www.readbyqxmd.com/read/28817603/expression-of-the-mhc-class-ii-in-triple-negative-breast-cancer-is-associated-with-tumor-infiltrating-lymphocytes-and-interferon-signaling
#11
In Ah Park, Seong-Hye Hwang, In Hye Song, Sun-Hee Heo, Young-Ae Kim, Won Seon Bang, Hye Seon Park, Miseon Lee, Gyungyub Gong, Hee Jin Lee
Tumor-infiltrating lymphocytes (TILs) have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC). Several mechanisms for TIL influx in TNBC have been elucidated. Major histocompatibility complex class II (MHC-II) is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28817184/the-influence-of-cytomegalovirus-on-expression-of-hla-g-and-its-ligand-kir2dl4-by-human-peripheral-blood-leucocyte-subsets
#12
Zaid Albayati, Ahmed Alyami, Suliman Alomar, Derek Middleton, Laura Bonnett, Sobia Aleem, Brian F Flanagan, Stephen E Christmas
HLA-G is a non-classical class I HLA antigen, normally expressed in high levels only on extravillous cytotrophoblast. It has immunosuppressive properties in pregnancy and has also been found to be upregulated on leucocytes in viral infection. In this study, proportions of all leucocyte subsets expressing HLA-G were found to be low in healthy subjects positive or negative for cytomegalovirus (CMV). Significantly greater proportions of CD4+CD69+ and CD56+ T cells expressed HLA-G compared to other T cells. However, following stimulation with CMV antigens or intact CMV, proportions of CD4+, CD8+, CD69+ and CD56+ T cells, and also B cells expressing HLA-G were significantly increased in CMV+ subjects...
August 17, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28817117/increased-tumor-infiltrating-cd45ra-ccr7-regulatory-t-cell-subset-with-immunosuppressive-properties-foster-gastric-cancer-progress
#13
Fang-Yuan Mao, Hui Kong, Yong-Liang Zhao, Liu-Sheng Peng, Weisan Chen, Jin-Yu Zhang, Ping Cheng, Ting-Ting Wang, Yi-Pin Lv, Yong-Sheng Teng, Xiao-Long Fu, Yu-Gang Liu, Xiao-Long Wu, Chuan-Jie Hao, Nan You, Ping Luo, Pei-Wu Yu, Quan-Ming Zou, Gang Guo, Yuan Zhuang
Regulatory T cells (Tregs) are major components of tumor-infiltrating immune cells with potent immunosuppressive properties in gastric cancer (GC) microenvironment. However, different subsets of the Tregs and their relevance to GC are unknown. Here, we found that patients with GC showed a significantly higher Tregs infiltration in tumors, and CD45RA(-)CCR7(-) Treg subset constituted most tumor-infiltrating Tregs. Tumor-infiltrating CD45RA(-)CCR7(-) Treg subset with an effector/memory phenotype accumulated in tumors and expressed low level of HLA-DR...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28815764/aligning-digital-cd8-scoring-and-targeted-next-generation-sequencing-with-pd-l1-expression-a-pragmatic-approach-in-early-stage-squamous-cell-lung-carcinoma
#14
Esther Conde, Alejandra Caminoa, Carolina Dominguez, Antonio Calles, Stefan Walter, Barbara Angulo, Elena Sánchez, Marta Alonso, Luis Jimenez, Luis Madrigal, Florentino Hernando, Julian Sanz-Ortega, Beatriz Jimenez, Pilar Garrido, Luis Paz-Ares, Javier de Castro, Susana Hernandez, Fernando Lopez-Rios
AIMS: To study PD-L1 expression, tumour-infiltrating T lymphocytes (TILs) and the molecular context in patients with early-stage squamous cell lung carcinomas (SCCs). METHODS AND RESULTS: The study included samples from 40 patients (discovery cohort) and 29 patients (validation cohort) diagnosed with early-stage SCC. PD-L1 immunohistochemistry (IHC) was performed with three commercially available clones (E1L3N, SP263 and SP142). CD8(+) TILs were scored with a digital algorithm...
August 16, 2017: Histopathology
https://www.readbyqxmd.com/read/28815584/maintenance-of-cd8-memory-t-lymphocytes-in-the-spleen-but-not-in-the-bone-marrow-is-dependent-on-proliferation
#15
Francesco Siracusa, Özen Sercan Alp, Patrick Maschmeyer, Mairi McGrath, Mir-Farzin Mashreghi, Shintaro Hojyo, Hyun-Dong Chang, Koji Tokoyoda, Andreas Radbruch
It is current belief that numbers of CD8 memory T lymphocytes in the memory phase of an immune response are maintained by homeostatic proliferation. Here we compare the proliferation of CD8 memory T lymphocytes, generated by natural infections and by intentional immunization, in spleen and in bone marrow. 50% of CD8 memory T lymphocytes in the spleen are eliminated by cyclophosphamide within 14 days, indicating that numbers of at least 50% of splenic CD8 memory T lymphocytes are maintained by proliferation...
August 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28815218/capturing-the-systemic-immune-signature-of-a-norovirus-infection-an-n-of-1-case-study-within-a-clinical-trial
#16
Antony J Cutler, Joao Oliveira, Ricardo C Ferreira, Ben Challis, Neil M Walker, Sarah Caddy, Jia Lu, Helen E Stevens, Deborah J Smyth, Marcin L Pekalski, Jane Kennet, Kara M D Hunter, Ian Goodfellow, Linda S Wicker, John A Todd, Frank Waldron-Lynch
BACKGROUND:  The infection of a participant with norovirus during the adaptive study of interleukin-2 dose on regulatory T cells in type 1 diabetes (DILT1D) allowed a detailed insight into the cellular and cytokine immune responses to this prevalent gastrointestinal pathogen. METHODS:  Serial blood, serum and peripheral blood mononuclear cell (PBMC) samples were collected pre-, and post-development of the infection. To differentiate between the immune response to norovirus and to control for the administration of a single dose of aldesleukin (recombinant interleukin-2, rIL-2) alone, samples from five non-infected participants administered similar doses were analysed in parallel...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28815045/tumor-derived-exosomes-induce-cd8-t-cell-suppressors
#17
Brian T Maybruck, Lukas W Pfannenstiel, Marcela Diaz-Montero, Brian R Gastman
BACKGROUND: The suppressive nature of immune cells in the tumor microenvironment plays a major role in regulating anti-tumor immune responses. Our previous work demonstrated that a soluble factor from tumor cells is able to induce a suppressor phenotype (SP) in human CD8(+) T cells typified by loss of CD27/CD28 expression and acquisition of a potent suppressor function. The present study hypothesized that the soluble mechanism that is inducing the SP in CD8(+) T cells are tumor-derived exosomes (TDEs)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28815044/agonist-anti-gitr-antibody-significantly-enhances-the-therapeutic-efficacy-of-listeria-monocytogenes-based-immunotherapy
#18
Rajeev Shrimali, Shamim Ahmad, Zuzana Berrong, Grigori Okoev, Adelaida Matevosyan, Ghazaleh Shoja E Razavi, Robert Petit, Seema Gupta, Mikayel Mkrtichyan, Samir N Khleif
BACKGROUND: We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4(+) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28814733/enhancing-immune-responses-to-cancer-vaccines-using-multi-site-injections
#19
Robert C Mould, Amanda W K AuYeung, Jacob P van Vloten, Leonardo Susta, Anthony J Mutsaers, James J Petrik, Geoffrey A Wood, Sarah K Wootton, Khalil Karimi, Byram W Bridle
For a vaccine to be effective it must induce a sufficiently robust and specific immune response. Multi-site injection protocols can increase the titers of rabies virus-neutralizing antibodies. Hypothetically, spreading a vaccine dose across multiple lymphatic drainage regions could also potentiate T cell responses. We used a replication-deficient adenovirus serotype 5-vectored cancer vaccine targeting the melanoma-associated antigen dopachrome tautomerase. Clinically, high numbers of tumor-infiltrating CD8(+) T cells are a positive prognostic indicator...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814601/il-15-complexes-induce-migration-of-resting-memory-cd8-t-cells-into-mucosal-tissues
#20
Ryan T Sowell, Josef W Goldufsky, Magdalena Rogozinska, Zurisaday Quiles, Yanxia Cao, Eliseo F Castillo, Alison Finnegan, Amanda L Marzo
IL-15 is an essential cytokine known to promote T cell survival and activate the effector function of memory phenotype CD8 T cells. Blocking IL-15 signals also significantly impacts tissue-specific effector and memory CD8 T cell formation. In this study, we demonstrate that IL-15 influences the generation of memory CD8 T cells by first promoting their accumulation into mucosal tissues and second by sustaining expression of Bcl-6 and T-bet. We show that the mechanism for this recruitment is largely dependent on mammalian target of rapamycin and its subsequent inactivation of FoxO1...
August 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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