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https://www.readbyqxmd.com/read/29777446/the-degree-of-hiv-1-amino-acid-variability-is-strictly-related-to-different-disease-progression-rates
#1
Rossana Scutari, Monica Faieta, Roberta D'Arrigo, Lavinia Fabeni, Cristina Mussini, Andrea Cossarizza, Claudio Casoli, Carlo Federico Perno, Valentina Svicher, Claudia Alteri, Stefano Aquaro
The aim of this study is to evaluate the amino acid variability of HIV-1 Gp41, C2-V3, and Nef in a group of patients characterized by different disease progression rates. HIV-1 sequences were collected from 19 Long term non progressor patients (LTNPs), 9 slow progressors (SPs), and 11 rapid progressors (RPs). Phylogenetic trees were estimated by MEGA 6. Differences in amino acid variability among sequences belonging to the 3 groups have been evaluated by amino acid divergence, Shannon entropy analysis, and the number of amino acid mutations (defined as amino acid variations compared with HxB2)...
May 17, 2018: Virus Genes
https://www.readbyqxmd.com/read/29775667/identification-of-novel-hla-a11-restricted-t-cell-epitopes-in-the-ebola-virus-nucleoprotein
#2
Dan Li, Pei Li, Nianping Song, Yuting Jiang, Yang Zeng, Guangyu Zhao, Yunzhi Fa, Huahu Ye, Yuchun Lone, Yusen Zhou, Shihui Sun, Lin Zeng
The Ebola virus (EBOV) is a very contagious virus that is highly fatal in humans and animals. The largest epidemic was in West Africa in 2014, in which over 11,000 people died. However, to date, there are no licensed vaccines against it. Studies show that CD4+ and CD8+ T-cell responses, especially cytotoxic T-lymphocyte (CTL) responses, play key roles in protecting individuals from EBOV infection. Since HLA-restricted epitope vaccines are likely to be effective and safe immunization strategies for infectious diseases, the present study screened for CTL epitopes in the EBOV-nucleoprotein that are restricted by HLA-A11 (a common allele in Chinese people)...
May 15, 2018: Microbes and Infection
https://www.readbyqxmd.com/read/29765252/triple-negative-and-her2-overexpressing-breast-cancer-cell-sialylation-impacts-tumor-microenvironment-t-lymphocyte-subset-recruitment-a-possible-mechanism-of-tumor-escape
#3
Christian Garbar, Corinne Mascaux, Yacine Merrouche, Armand Bensussan
Introduction: Breast cancers develop different patterns of sialylation to modulate their tumor-infiltrating lymphocyte (TIL) environment. We studied the relationship between α-2,6 sialyltransferases and the TIL in different breast cancer molecular subgroups. Materials and methods: Immunohistochemical preparations were made from 39 luminal (LUM), 13 human epidermal growth factor receptor 2-overexpressing (HER2) and 47 triple-negative (TN) breast carcinomas. Targeted proteins included ST6Gal-I, ST6Gal-II, ST6GalNac-I, CD8, CD4 and granzyme-B in both cytotoxic T lymphocytes and NK lymphocytes (CTL/NK)...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29764836/subcellular-localization-of-antigen-dictates-delivery-of-cd4-t-cell-help-for-the-ctl-response-upon-therapeutic-dna-vaccination-into-the-skin
#4
Nikolina Bąbała, Astrid Bovens, Evert de Vries, Victoria Iglesias-Guimarais, Tomasz Ahrends, Matthew F Krummel, Jannie Borst, Adriaan D Bins
In a mouse model of therapeutic DNA vaccination, we studied how the subcellular localization of vaccine protein impacts antigen delivery to professional antigen presenting cells (pAPCs) and efficiency of CTL priming. Cytosolic, membrane-bound, nuclear, and secretory versions of ZsGreen fluorescent protein, conjugated to MHC class I and -II ovalbumin (OVA) epitopes were expressed in keratinocytes by DNA vaccination into the skin. ZsGreen-OVA versions reached B cells in the skin-draining lymph node (dLN) that proved irrelevant for CTL priming...
May 15, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29739434/gastric-cancer-vaccines-synthesized-using-a-tlr7-agonist-and-their-synergistic-antitumor-effects-with-5-fluorouracil
#5
Xiaodong Wang, Yu Liu, Yuwen Diao, Ningning Gao, Yanyan Wan, Jingjing Zhong, Huali Zheng, Zhulin Wang, Guangyi Jin
BACKGROUND: Vaccines play increasingly important roles in cancer treatment due to their advantages of effective targeting and few side effects. Our laboratory has attempted to construct vaccines by conjugating TLR7 agonists with tumor-associated antigens. Furthermore, immunochemotherapy has recently become an appealing approach to cancer therapy. 5-fluorouracil (5-FU), a commonly used chemotherapeutic agent, can reportedly potently and selectively kill tumor-associated MDSCs in vivo. METHODS: Gastric cancer vaccines were synthesized by the covalent attachment of our TLR7 agonist with the gastric cancer antigen MG7-Ag tetra-epitope, leading to T7 - ML (linear tetra-epitope) and T7 - MB (branched tetra-epitope)...
May 8, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29710479/antigen-adjuvant-effects-of-icariin-in-enhancing-tumor-specific-immunity-in-mastocytoma-bearing-dba-2j-mice
#6
Xiaodi Zhang, Zhichen Kang, Qingjie Li, Jin Zhang, Sha Cheng, Hao Chang, Shanshan Wang, Shufang Cao, Tie Li, Jiawei Li, Yishan Wang, Yu Song, Hao Yu
Cancer immunotherapy has attracted much attention in recent years because of the ability of immune system to identify tumor cells and limit their growth. Icariin (ICA) is a natural flavonoid glucoside isolated from Epimedium plants and has shown a variety of pharmacological activities such as anti-inflammatory effects, immunological regulation and anticancer potency. Furthermore, it has immunoadjuvant effects on enhancing Th1-immune response, suggesting that ICA may serve as an adjuvant for cancer immunotherapy...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29700809/the-opposing-roles-of-cd4-t-cells-in-anti-tumor-immunity
#7
REVIEW
Tomasz Ahrends, Jannie Borst
Cancer immunotherapy focuses mainly on anti-tumor activity of CD8+ cytotoxic T lymphocytes (CTLs). CTLs can directly kill all tumor cell types, provided that they carry recognizable antigens. However, CD4+ T cells also play important roles in anti-tumor immunity. CD4+ T cells can either suppress or promote anti-tumor CTL response, both in secondary lymphoid organs or in the tumor. In this review, we highlight opposing mechanisms of conventional (Tconv) and regulatory (Treg) T cells at both sites. We outline how current cancer immunotherapy strategies affect both subsets and how selective modulation of each subset is important to maximize the clinical response of cancer patients...
April 27, 2018: Immunology
https://www.readbyqxmd.com/read/29615718/genetic-abrogation-of-immune-checkpoints-in-antigen-specific-cytotoxic-t-lymphocyte-as-a-potential-alternative-to-blockade-immunotherapy
#8
Chi Zhang, Yanchun Peng, Philip Hublitz, Haokang Zhang, Tao Dong
T cell function can be compromised during chronic infections or through continuous exposure to tumor antigens by the action of immune checkpoint receptors, such as programmed cell death protein 1 (PD-1). Systemic administration of blocking antibodies against the PD-1 pathway can restore T cell function, and has been approved for the treatment of several malignancies, although there is a risk of adverse immune-related side-effects. We have developed a method for generating gene knockouts in human antigen (Ag)-specific cytotoxic T-Lymphocyte (CTLs) using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome editing...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29593044/control-of-hiv-1-pathogenesis-in-viremic-nonprogressors-is-independent-of-gag-specific-ctl-responses
#9
Maria Salgado, Albert Garcia-Minambres, Judith Dalmau, Esther Jiménez-Moyano, Pompeyo Viciana, Belén Alejos, Bonaventura Clotet, Julia G Prado, Javier Martinez-Picado
Viremic nonprogressors (VNP) constitute a very scarce group of untreated HIV-1-infected individuals who maintain stable CD4+ T cell-counts despite high levels of HIV-1 replication. The specific factors associated to this atypical control of the HIV infection are poorly described. Since specific T-cell responses seem to be one of the main causes of HIV-1 control in elite controllers, herein we study if HIV-1 Gag-specific cytotoxic T lymphocyte (CTL) responses could also modulate disease control in VNP.We characterized immune responses from four VNPs compared to five subjects with standard progression (SP) during the first years of HIV-1 infection...
March 28, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29581358/deregulated-mucosal-immune-surveillance-through-gut-associated-regulatory-t-cells-and-pd-1-t-cells-in-human-colorectal-cancer
#10
Hanae Fujimoto, Yoriko Saito, Kenoki Ohuchida, Eiryo Kawakami, Saera Fujiki, Takashi Watanabe, Rintaro Ono, Akiko Kaneko, Shinsuke Takagi, Yuho Najima, Atsushi Hijikata, Lin Cui, Takashi Ueki, Yoshinao Oda, Shohei Hori, Osamu Ohara, Masafumi Nakamura, Takashi Saito, Fumihiko Ishikawa
Disturbed balance between immune surveillance and tolerance may lead to poor clinical outcomes in some malignancies. In paired analyses of adenocarcinoma and normal mucosa from 142 patients, we found a significant increase of the CD4/CD8 ratio and accumulation of regulatory T cells (Tregs) within the adenocarcinoma. The increased frequency of Tregs correlated with the local infiltration and extension of the tumor. There was concurrent maturation arrest, upregulation of programmed death-1 expression, and functional impairment in CD8+ T cells (CTLs) isolated from the adenocarcinoma...
March 26, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29577371/role-of-t-bet-the-master-regulator-of-th1-cells-in-the-cytotoxicity-of-murine-cd4-t-cells
#11
Koji Eshima, Kana Misawa, Chihiro Ohashi, Kazuya Iwabuchi
Although CD4+ T cells are generally regarded as helper T cells, some activated CD4+ T cells exert cytotoxicity. Since CD4+ cytotoxic T lymphocytes (CTLs) often secrete IFN-γ, CTL activity among CD4+ T cells may be attributable to Th1 cells, where a T-box family molecule, T-bet serves as the "master regulator". However, although the essential contribution of T-bet to the expression of IFN-γ has been well-documented, it remains unclear if T-bet is involved in CD4+ T cell-mediated cytotoxicity. In this study, in order to investigate the ability of T-bet to confer cytolytic activity on CD4+ T cells, we introduced the T-bet gene into non-cytocidal CD4+ T cell lines and analyzed their cytolytic function...
March 25, 2018: Microbiology and Immunology
https://www.readbyqxmd.com/read/29488118/involvement-of-cd8-t-cells-in-the-development-of-renal-hemorrhage-in-a-mouse-model-of-hemorrhagic-fever-with-renal-syndrome
#12
Kenta Shimizu, Kumiko Yoshimatsu, Midori Taruishi, Yoshimi Tsuda, Jiro Arikawa
Hemorrhagic fever with renal syndrome (HFRS) is caused by hantavirus infection. Although host immunity is thought to be involved in the pathogenesis of HFRS, the mechanism remains to be elucidated. A mouse model of HFRS, which showed renal hemorrhage similar to that seen in patients, has been developed previously. In this study, we aimed to clarify whether CD4+ and CD8+ T cells are involved in the development of renal hemorrhage in the mouse model. At 2 days before virus inoculation, CD4+ or CD8+ T cells in 6-week-old BALB/c mice were depleted by administration of antibodies...
February 27, 2018: Archives of Virology
https://www.readbyqxmd.com/read/29487385/histone-deacetylase-hdac-inhibitor-acy241-enhances-anti-tumor-activities-of-antigen-specific-central-memory-cytotoxic-t-lymphocytes-against-multiple-myeloma-and-solid-tumors
#13
Jooeun Bae, Teru Hideshima, Yu-Tzu Tai, Yan Song, Paul Richardson, Noopur Raje, Nikhil C Munshi, Kenneth C Anderson
Histone deacetylases (HDAC) are therapeutic targets in multiple cancers. ACY241, an HDAC6 selective inhibitor, has shown anti-multiple myeloma (MM) activity in combination with immunomodulatory drugs and proteasome inhibitors. Here we show ACY241 significantly reduces the frequency of CD138+ MM cells, CD4+ CD25+ FoxP3+ regulatory T cells, and HLA-DRLow/- CD11b+ CD33+ myeloid-derived suppressor cells; and decreases expression of PD1/PD-L1 on CD8+ T cells and of immune checkpoints in bone marrow cells from myeloma patients...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29485973/self-adjuvanting-nanoemulsion-targeting-dendritic-cell-receptor-clec9a-enables-antigen-specific-immunotherapy
#14
Bijun Zeng, Anton Pj Middelberg, Adrian Gemiarto, Kelli MacDonald, Alan G Baxter, Meghna Talekar, Davide Moi, Kirsteen M Tullett, Irina Caminschi, Mireille H Lahoud, Roberta Mazzieri, Riccardo Dolcetti, Ranjeny Thomas
Non-antigen-specific stimulatory cancer immunotherapies are commonly complicated by off-target effects. Antigen-specific immunotherapy, combining viral tumor antigen or personalized neoepitopes with immune targeting, offers a solution. However, the lack of flexible systems targeting tumor antigens to cross-presenting dendritic cells (DCs) limits clinical development. Although antigen-anti-Clec9A mAb conjugates target cross-presenting DCs, adjuvant must be codelivered for cytotoxic T lymphocyte (CTL) induction...
May 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29467598/an-attempt-to-induce-an-immunomodulatory-effect-in-rowers-with-spirulina-extract
#15
RANDOMIZED CONTROLLED TRIAL
Artur Juszkiewicz, Piotr Basta, Elżbieta Petriczko, Bogusław Machaliński, Jerzy Trzeciak, Karolina Łuczkowska, Anna Skarpańska-Stejnborn
Background: The aim of this study was to analyze the response of selected components of the immune system in rowers to maximal physical exercise, and to verify if this response can be modulated by supplementation with spirulina (cyanobacterium Spirulina platensis ) . Method: The double-blind study included 19 members of the Polish Rowing Team. The subjects were randomly assigned to the supplemented group ( n  = 10), receiving 1500 mg of spirulina extract for 6 weeks, or to the placebo group ( n  = 9)...
2018: Journal of the International Society of Sports Nutrition
https://www.readbyqxmd.com/read/29434784/effects-of-intratumoral-injection-of-immunoactivator-after-microwave-ablation-on-antitumor-immunity-in-a-mouse-model-of-hepatocellular-carcinoma
#16
Hao Wu, Bin Chen, Baogang Peng
This study investigated the effects of intratumoral injection of immunoactivator after microwave ablation on antitumor immunity in a mouse model of hepatocellular carcinoma. Hepatocellular carcinoma cell line Hepa1-6 was subcutaneously injected into C57/B6 mice to establish a mouse model of hepatocellular carcinoma. When tumor diameter reached 8 mm, microwave ablation was performed for 3 min with temperature controlled at 55°C. Cytokine sustained-release microspheres (CytoMPS) containing human interleukin-2 (hIL-2) and mouse granulocyte macrophage colony-stimulating factor (mGM-CSF) were injected into the tumor of mice in the experimental group (n=5) at 3, 7 and 14 days after ablation, while sustained-release microspheres containing no cytokine were used in the control group (n=5)...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29422894/the-b-cell-follicle-in-hiv-infection-barrier-to-a-cure
#17
REVIEW
Matthew P Bronnimann, Pamela J Skinner, Elizabeth Connick
The majority of HIV replication occurs in secondary lymphoid organs (SLOs) such as the spleen, lymph nodes, and gut-associated lymphoid tissue. Within SLOs, HIV RNA+ cells are concentrated in the B-cell follicle during chronic untreated infection, and emerging data suggest that they are a major source of replication in treated disease as well. The concentration of HIV RNA+ cells in the B-cell follicle is mediated by several factors. Follicular CD4+ T-cell subsets including T-follicular helper cells and T-follicular regulatory cells are significantly more permissive to HIV than extrafollicular subsets...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29415817/heterologous-human-rat-her2-specific-exosome-targeted-t-cell-vaccine-stimulates-potent-humoral-and-ctl-responses-leading-to-enhanced-circumvention-of-her2-tolerance-in-double-transgenic-hla-a2-her2-mice
#18
Yufeng Xie, Jie Wu, Aizhang Xu, Shahid Ahmeqd, Amer Sami, Rajni Chibbar, Andrew Freywald, Changyu Zheng, Jim Xiang
DNA vaccines composed of heterologous human HER2 and rat neu sequences induce stronger antibody response and protective antitumor immunity than either HER2 or neu DNA vaccines in transgenic mice. We previously developed HER2-specific exosome-targeted T-cell vaccine HER2-TEXO capable of stimulating HER2-specific CD8+ T-cell responses, but only leading to partial protective immunity in double-transgenic HLA-A2/HER2 mice with self-immune tolerance to HER2. Here, we constructed an adenoviral vector AdVHuRt expressing HuRt fusion protein composed of NH2 -HER21-407 (Hu) and COOH-neu408-690 (Rt) fragments, and developed a heterologous human/rat HER2-specific exosome-targeted T-cell vaccine HuRt-TEXO using polyclonal CD4+ T-cells uptaking exosomes released by AdVHuRt -transfected dendritic cells...
March 7, 2018: Vaccine
https://www.readbyqxmd.com/read/29408905/splenic-macrophages-are-required-for-protective-innate-immunity-against-west-nile-virus
#19
Marianne A Bryan, Daniela Giordano, Kevin E Draves, Richard Green, Michael Gale, Edward A Clark
Although the spleen is a major site for West Nile virus (WNV) replication and spread, relatively little is known about which innate cells in the spleen replicate WNV, control viral dissemination, and/or prime innate and adaptive immune responses. Here we tested if splenic macrophages (MΦs) were necessary for control of WNV infection. We selectively depleted splenic MΦs, but not draining lymph node MΦs, by injecting mice intravenously with clodronate liposomes several days prior to infecting them with WNV...
2018: PloS One
https://www.readbyqxmd.com/read/29407585/regulatory-t-cell-inhibition-by-dasatinib-is-associated-with-natural-killer-cell-differentiation-and-a-favorable-molecular-response-the-final-results-of-the-d-first-study
#20
Yuho Najima, Chikashi Yoshida, Noriyoshi Iriyama, Shin Fujisawa, Hisashi Wakita, Shigeru Chiba, Shinichiro Okamoto, Kimihiro Kawakami, Naoki Takezako, Takashi Kumagai, Kazuma Ohyashiki, Jun Taguchi, Shingo Yano, Tadahiko Igarashi, Yasuji Kouzai, Satoshi Morita, Junichi Sakamoto, Hisashi Sakamaki, Koiti Inokuchi
We evaluated the effects of regulatory T cell (Treg) inhibition during dasatinib treatment on the anticancer immune response, particularly on natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Fifty-two newly diagnosed Japanese patients with chronic myeloid leukemia (CML) in the chronic phase were enrolled in the D-first study; all received 100 mg of dasatinib once daily and were followed for at least 36 months. The cumulative deep molecular response (DMR, MR4) rate was 65% by 36 months; the 3-year overall survival was 96%...
March 2018: Leukemia Research
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