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https://www.readbyqxmd.com/read/28930685/human-tissue-resident-memory-t-cells-are-defined-by-core-transcriptional-and-functional-signatures-in-lymphoid-and-mucosal-sites
#1
Brahma V Kumar, Wenji Ma, Michelle Miron, Tomer Granot, Rebecca S Guyer, Dustin J Carpenter, Takashi Senda, Xiaoyun Sun, Siu-Hong Ho, Harvey Lerner, Amy L Friedman, Yufeng Shen, Donna L Farber
Tissue-resident memory T cells (TRMs) in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRMs remain unclear. Here, we use a unique human tissue resource to determine whether human tissue memory T cells constitute a distinct subset in diverse mucosal and lymphoid tissues. We identify a core transcriptional profile within the CD69(+) subset of memory CD4(+) and CD8(+) T cells in lung and spleen that is distinct from that of CD69(-) TEM cells in tissues and circulation and defines human TRMs based on homology to the transcriptional profile of mouse CD8(+) TRMs...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28929835/dab389il-2-recombinant-fusion-toxin-effect-on-lymphocyte-and-macrophage-producing-cytokine-subpopulation-cells-in-experimentally-induced-demyelinating-disease-in-mice
#2
Mahendra K Bhopale, Brendan Hilliard, Cris S Constantinescu, S Michael Phillips, Abdolmohamad Rostami
CONTEXT: We have reported previously that DAB389IL-2 recombinant fusion toxin targets IL-2R bearing CD4(+) cells, and suppresses demyelinating disease in acute (A) - and chronic (C) - experimental autoimmune encephalomyelitis (EAE) animal models of multiple sclerosis. OBJECTIVES: The present study was undertaken to investigate the effect of DAB389IL-2 treatment on various cytokine-secreting cell populations in A-EAE and C-EAE mice. MATERIALS AND METHODS: The effects of DAB389IL-2 at doses of 200-, 800-, or 1600 kU administered i...
September 20, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28929596/hypogammaglobulinemia-in-children-a-warning-sign-to-look-deeply
#3
Karina Mescouto de Melo, Maria Isabel de Moraes-Pinto, Luís E C Andrade, Reinaldo Salomão, Milena K C Brunialti, Vanessa S Ferreira, Beatriz T Costa-Carvalho
This study investigated phenotypic and functional characteristics of lymphocytes in children with common variable immunodeficiency (CVID) and unclassified hypogammaglobulinemia (UH), as well as B-cell subsets in non-consanguineous parents. Blood samples of 30 children, CVID (n = 9), UH (n = 9), healthy donors HD (n = 12), and 19 adults (parents and controls) were labeled by a combination of surface markers to identify CD4, CD8 T-cell and B-cell subpopulations. T-cell cytokine production in children was analyzed in vitro after stimulation with phytohemagglutinin (PHA) and tetanus toxoid...
October 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28929455/role-of-mast-cells-in-regulation-of-t-cell-responses-in-experimental-and-clinical-settings
#4
REVIEW
Daniel Elieh Ali Komi, Korneel Grauwet
Mast cells secrete a wide spectrum of stored or newly synthesized pro-inflammatory, anti-inflammatory, and/or immunosuppressive mediators and express several costimulatory and inhibitory surface molecules. Mast cells finely tune activities of T cells, B cells, and regulatory cells and effectively contribute to the development of different T cell-associated responses by influencing their recruitment, activation, proliferation, and differentiation. The interaction between mast cells and T cells, with regard to cellular functionality and immune responses, can be assessed in both activating and inhibitory regulations...
September 19, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28929123/in-vitro-immunomodulatory-activity-of-a-transition-state-analog-inhibitor-of-human-purine-nucleoside-phosphorylase-in-cutaneous-leishmaniasis
#5
Natália Barbosa Carvalho, Fernanda Ventin de Oliveira Prates, Rafael de Castro da Silva, Mayra Elizabeth Ferreira Dourado, Camila Farias Amorim, Paulo Roberto Lima Machado, Fernanda Grendene Pacheco, Temis Weber Furlanetto Corte, Pablo Machado, Diógenes Santiago Santos, Edgar Marcelino de Carvalho
Cutaneous leishmaniasis (CL) is the most common clinical form of American tegumentary leishmaniasis caused by Leishmania (Viannia) braziliensis. CL is associated with a strong Th1 immune response. This exacerbated inflammatory response is correlated with severity of disease and delays the healing time of the ulcer. The fourth-generation immucillin derivative (DI4G), a potent inhibitor of purine nucleoside phosphorylase, has been proposed as a promising agent in the treatment of diseases associated with T cell activation...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28928792/garidisan-improving-the-quality-of-ulcer-healing-in-rats-with-ulcerative-colitis
#6
Lin Wang, Wei-Zhi Liu, Ling-Yan Pei, Yu-Shi Ke, Jian Cui, Shu-Chun Li
Garidisan, commonly used in Mongolia to treat ulcerative colitis (UC), contains wild poppy and Artemisia frigida Willd. Clinical evidence shows that Garidisan can effectively treat UC and that recurrence is low. Thus, we evaluated the effects of Garidisan on ulcer healing quality and the regulation of immune balance in rats with experimental UC. UC was induced by immunization with TNBS and Garidisan significantly reduced DAI, CMDI, and HS. H&E staining, SEM, and VG staining showed that Garidisan repaired damaged intestinal mucosa and significantly reduced expression of ICAM-1 and CD105 in regenerated tissues of UC rats...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28928286/hpv-integration-in-hnscc-correlates-with-survival-outcomes-immune-response-signatures-and-candidate-drivers
#7
Lada A Koneva, Yanxiao Zhang, Shama Virani, Pelle B Hall, Jonathan B McHugh, Douglas B Chepeha, Gregory Wolf, Thomas E Carey, Laura S Rozek, Maureen A Sartor
The incidence of human papillomavirus (HPV)-related oropharynx cancer has steadily increased over the past two decades, and now represents a majority of oropharyngeal cancer cases. Integration of the HPV genome into the host genome is a common event during carcinogenesis that has clinically-relevant effects if the viral early genes are transcribed. Understanding the impact of HPV integration on clinical outcomes of head and neck squamous cell carcinoma (HNSCC) is critical for implementing de-escalated treatment approaches for HPV-positive HNSCC patients...
September 19, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28926641/impact-of-monotherapy-on-hiv-1-reservoir-immune-activation-and-co-infection-with-epstein-barr-virus
#8
Maria Raffaella Petrara, Anna Maria Cattelan, Lolita Sasset, Riccardo Freguja, Francesco Carmona, Silvia Sanavia, Marisa Zanchetta, Paola Del Bianco, Anita De Rossi
OBJECTIVES: Although monotherapy (mART) effectiveness in maintaining viral suppression and CD4 cell count has been extensively examined in HIV-1-infected patients, its impact on HIV-1 reservoir, immune activation, microbial translocation and co-infection with Epstein-Barr Virus (EBV) is unclear. METHODS: This retrospective study involved 32 patients who switched to mART; patients were studied at baseline, 48 and 96 weeks after mART initiation. Thirty-two patients who continued combined antiretroviral therapy (cART) over the same period of time were included in the study...
2017: PloS One
https://www.readbyqxmd.com/read/28926357/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#9
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
September 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28925793/sequential-administration-of-mva-based-vaccines-and-pd-1-pd-l1-blocking-antibodies-confers-measurable-benefits-on-tumor-growth-and-survival-preclinical-studies-with-mva-%C3%AE-gal-and-mva-muc1-tg4010-in-a-murine-tumor-model
#10
Christelle Remy-Ziller, Christine Thioudellet, Julie Hortelano, Murielle Gantzer, Virginie Nourtier, Marie-Christine Claudepierre, Benoit Sansas, Xavier Préville, Kaïdre Bendjama, Eric Quemeneur, Karola Rittner
TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal...
September 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28923683/a-hydrogel-matrix-prolongs-persistence-and-promotes-specific-localization-of-an-oncolytic-adenovirus-in-a-tumor-by-restricting-nonspecific-shedding-and-an-antiviral-immune-response
#11
Bo-Kyeong Jung, Eonju Oh, JinWoo Hong, Yunki Lee, Ki Dong Park, Chae-Ok Yun
Currently, intratumoral injection of an oncolytic adenovirus (Ad) is the conventional administration route in clinical trials. Nonetheless, the locally administered Ad disseminates to the surrounding nontarget tissues and has short biological activity due to immunogenicity of Ad, thus necessitating multiple injections to achieve a sufficient therapeutic index. In the present study, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-expressing oncolytic Ad (oAd-TRAIL) was encapsulated in a gelatin hydrogel (oAd-TRAIL/gel) to enhance and prolong antitumor efficacy of the virus after a single intratumoral injection...
September 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28923424/depletion-of-regulatory-t-cells-by-anti-icos-antibody-enhances-anti-tumor-immunity-of-tumor-cell-vaccine-in-prostate-cancer
#12
Lijun Mo, Qianmei Chen, Xinji Zhang, Xiaojun Shi, Lili Wei, Dianpeng Zheng, Hongwei Li, Jimin Gao, Jinlong Li, Zhiming Hu
ICOS(+)Treg cells exert important immunosuppressive effects in tumor immunity. We adopt a combination approach of ICOS(+)Treg cells depletion with tumor cell vaccine to evaluate anti-tumor immunity in mouse prostate cancer model. Streptavidin (SA)-mGM-CSF surface-modified RM-1 cells were prepared as the vaccine and the mouse subcutaneous prostate tumor model was used to evaluate the immunity. Tumor growth, flow cytometry, immunohistochemistry, immunofluorescence and enzyme linked immunosorbent assay (ELISA) were performed to evaluate the therapeutic effects...
September 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28923392/mitochondrial-depletion-in-cd4-and-cd19-peripheral-lymphocytes-in-early-stage-alzheimer-s-disease
#13
Gökhan Terzioğlu, Burcu Örmeci, Özlem Türksoy, Ceyhun Sayman, Nilgün Çınar, Gökçen Akar Öztürk, Gülderen Yanıkkaya Demirel
Alzheimer's disease (AD) may be associated with mitochondrial defects. The aim of the present study was to investigate changes in mitochondrial abundance in peripheral lymphocytes of early and late stage AD patients. We analysed levels of mitochondrial DNA (mtDNA) and mean fluorescence intensity (MFI) of the mitochondria-specific antibody 113-1 in CD4(+), CD8(+), CD19(+) and CD56(+) peripheral lymphocytes of early and late stage AD by quantitative real-time PCR and flow cytometry, respectively. In early stage AD, the levels of mtDNA were significantly decreased in CD4(+), CD19(+) and CD56(+) peripheral lymphocytes while the MFI of 113-1 staining was significantly decreased in CD4(+) and CD19(+) cells...
September 15, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28923066/data-integration-from-pathology-slides-for-quantitative-imaging-of-multiple-cell-types-within-the-tumor-immune-cell-infiltrate
#14
Zhaoxuan Ma, Stephen L Shiao, Emi J Yoshida, Steven Swartwood, Fangjin Huang, Michael E Doche, Alice P Chung, Beatrice S Knudsen, Arkadiusz Gertych
BACKGROUND: Immune cell infiltrates (ICI) of tumors are scored by pathologists around tumor glands. To obtain a better understanding of the immune infiltrate, individual immune cell types, their activation states and location relative to tumor cells need to be determined. This process requires precise identification of the tumor area and enumeration of immune cell subtypes separately in the stroma and inside tumor nests. Such measurements can be accomplished by a multiplex format using immunohistochemistry (IHC)...
September 18, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#15
Hua Zhu, Song Gu, Minzhi Yin, Min Shi, Chao Xin, Jianmin Zhu, Jing Wang, Siqi Huang, Chenjie Xie, Jing Ma, Ci Pan, Jingyan Tang, Min Xu, Xue-Feng Bai
BACKGROUND: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors. PROCEDURE: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28921767/expansion-of-cd4-phenotype-among-cd160-receptor-expressing-lymphocytes-in-murine-pregnancy
#16
Matyas Meggyes, Laszlo Szereday, Pal Jakso, Barbara Bogar, Agnes Bogdan, Jasper Nörenberg, Eva Miko, Aliz Barakonyi
PROBLEM: CD160, a cell surface co-receptor, is capable of up- or downregulating cell proliferation, cytotoxicity or cytokine production on lymphocytes. Our aim was to investigate CD160(+) lymphocytes in the periphery and at the maternal-foetal interface during murine pregnancy. METHOD OF STUDY: CD4(+) , CD8(+) and gamma/delta T-cell phenotype, TIM3 co-expression and cytotoxic activity of CD160(+) lymphocytes of pregnant BALB/c mice were analysed by flow cytometry...
September 16, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28920615/the-phenolic-profiles-of-radix-tetrastigma-after-solid-phase-extraction-spe-and-their-antitumor-effects-and-antioxidant-activities-in-h22-tumor-bearing-mice
#17
Yong Sun, Rong Tsao, Fang Chen, Hongyan Li, Han Peng, Li Jiang, Yuhuan Chen, Zeyuan Deng
Radix Tetrastigma (RT), a herbal medicine and functional food in China, showed strong antiproliferative activities in vitro. However, the effects and the underlying mechanism of phenolic-rich extract of RT in H22 tumor-bearing mice are still unknown. Thus, the phenolic profiles and antitumor/antioxidant activities of a solid phase extraction (SPE) semi-purified extract of RT were investigated by a combination of chemical assays, LC-QTOF-MS/LC-QqQ-MS techniques and a tumor-bearing mice model. As a result, the total phenolic/flavonoid contents (TPC/TFC) and 24 individual phenolics were identified and quantified, which showed higher contents than that of crude extract...
September 18, 2017: Food & Function
https://www.readbyqxmd.com/read/28919508/pro-inflammatory-chitosan-poly-%C3%AE-glutamic-acid-nanoparticles-modulate-human-antigen-presenting-cells-phenotype-and-revert-their-pro-invasive-capacity
#18
Flávia Castro, Marta L Pinto, Andreia M Silva, Catarina L Pereira, Graciosa Q Teixeira, Maria Gomez-Lazaro, Susana G Santos, Mário A Barbosa, Raquel M Gonçalves, Maria J Oliveira
Anticancer immune responses depend on efficient presentation of tumor antigens and co-stimulatory signals provided by antigen-presenting cells (APCs). However, it is described that immature dendritic cells (DCs) and macrophages at the tumor site may have an immunosuppressive profile, which limits the activity of effector T cells and supports tumor progression. Therapeutic targeting of these innate immune cells, either aiming at their elimination or re-polarization towards an immunostimulatory profile, has been pointed as an attractive approach to control tumor progression...
September 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28918411/combining-cd4-recovery-and-cd4-cd8-ratio-restoration-as-an-indicator-for-evaluating-the-outcome-of-continued-antiretroviral-therapy-an-observational-cohort-study
#19
Shui Shan Lee, Ngai Sze Wong, Bonnie Chun Kwan Wong, Ka Hing Wong, Kenny Chi Wai Chan
OBJECTIVES: Immune recovery following highly active antiretroviral therapy (HAART) is commonly assessed by the degree of CD4 reconstitution alone. In this study, we aimed to assess immune recovery by incorporating both CD4 count and CD4:CD8 ratio. DESIGN: Observational cohort study SETTING AND PARTICIPANTS: Clinical data from Chinese HIV-positive patients attending the largest HIV service in Hong Kong and who had been on HAART for ≥4 years were accessed. MAIN OUTCOME MEASURES: Optimal immune outcome was defined as a combination of a CD4 count ≥500/μL and a CD4:CD8 ratio ≥0...
September 15, 2017: BMJ Open
https://www.readbyqxmd.com/read/28918288/th9-cells-promote-antitumor-immunity-via-il-9-and-il-21-and-demonstrate-atypical-cytokine-expression-in-breast-cancer
#20
Fa-Ping You, Jian Zhang, Tao Cui, Rui Zhu, Chong-Qing Lv, Hai-Tao Tang, Di-Wen Sun
Breast cancer is a major cause of cancer-related death in women. Antitumor T cell responses play critical therapeutic roles, including direct cytotoxicity mediated by CD8(+) T cells and immunomodulatory roles mediated by CD4(+) T cells. The IL-9-expressing Th9 cells are recently found to present antitumor immunity in melanoma and lung adenocarcinoma. In this study, we found that IL-9 expression in the serum and in circulating CD4(+) T cells were significantly upregulated in breast cancer patients compared to healthy controls...
September 14, 2017: International Immunopharmacology
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