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https://www.readbyqxmd.com/read/28922790/the-balance-between-cytotoxic-t-cell-lymphocytes-and-immune-checkpoint-expression-in-the-prognosis-of-colon-tumors
#1
Laetitia Marisa, Magali Svrcek, Ada Collura, Etienne Becht, Pascale Cervera, Kristell Wanherdrick, Olivier Buhard, Anastasia Goloudina, Vincent Jonchère, Janick Selves, Gerard Milano, Dominique Guenot, Romain Cohen, Chrystelle Colas, Pierre Laurent-Puig, Sylviane Olschwang, Jérémie H Lefèvre, Yann Parc, Valérie Boige, Côme Lepage, Thierry André, Jean-François Fléjou, Valentin Dérangère, François Ghiringhelli, Aurélien de Reynies, Alex Duval
Background: Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore. Methods: The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI)...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28921946/biomimetic-magnetosomes-as-versatile-artificial-antigen-presenting-cells-to-potentiate-t-cell-based-anticancer-therapy
#2
Qianmei Zhang, Wei Wei, Peiling Wang, Liping Zuo, Feng Li, Jin Xu, Xiaobo Xi, Xiaoyong Gao, Guanghui Ma, Hai-Yan Xie
Adoptive T-cell transfer for cancer therapy relies on both effective ex vivo T cell expansion and in vivo targeting performance. One promising but challenging method for accomplishing this purpose is to construct multifunctional artificial antigen-presenting cells (aAPCs). We herein developed biomimetic magnetosomes as versatile aAPCs, wherein magnetic nanoclusters were coated with azide-engineered leucocyte membranes and then decorated with T-cell stimuli through copper-free click chemistry. These novel nano aAPCs not only exhibited high performance for antigen-specific cytotoxic T cell (CTL) expansion and stimulation but also visually and effectively guided reinfused CTLs to tumor tissues through magnetic resonance imaging and magnetic control...
September 18, 2017: ACS Nano
https://www.readbyqxmd.com/read/28921501/immunological-tolerance-to-lcmv-antigens-differently-affects-control-of-acute-and-chronic-virus-infection-in-mice
#3
Christina Woopen, Tobias Straub, Oliver Schweier, Ulrike Aichele, Katharina Düker, Thomas Boehm, Hanspeter Pircher
Cytotoxic T lymphocytes (CTLs) play a key role in the control of lymphocytic choriomeningitis virus (LCMV) infection. In C57BL/6 mice (H-2(b) ), the CTL response is mainly directed against epitopes from the LCMV glycoprotein (GP) and the nucleoprotein (NP) which represent the two major viral proteins. The role of GP- versus NP-derived epitopes for viral clearance was examined using transgenic (tg) mice ubiquitously expressing LCMV GP and NP, respectively. These mice lack GP- or NP-specific CTLs and show decreased levels of GP- or NP-specific antibodies as a result of tolerance induction...
August 11, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28920002/ep4-antagonism-by-e7046-diminishes-myeloid-immunosuppression-and-synergizes-with-treg-reducing-il-2-diphtheria-toxin-fusion-protein-in-restoring-anti-tumor-immunity
#4
Diana I Albu, Zichun Wang, Kuan-Chun Huang, Jiayi Wu, Natalie Twine, Sarah Leacu, Christy Ingersoll, Lana Parent, Winnie Lee, Diana Liu, Renee Wright-Michaud, Namita Kumar, Galina Kuznetsov, Qian Chen, Wanjun Zheng, Kenichi Nomoto, Mary Woodall-Jappe, Xingfeng Bao
Reprogramming of immunosuppressive tumor microenvironment (TME) by targeting alternatively activated tumor associated macrophages (M2TAM), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Tregs), represents a promising strategy for developing novel cancer immunotherapy. Prostaglandin E2 (PGE2), an arachidonic acid pathway metabolite and mediator of chronic inflammation, has emerged as a powerful immunosuppressor in the TME through engagement with one or more of its 4 receptors (EP1-EP4). We have developed E7046, an orally bioavailable EP4-specific antagonist and show here that E7046 has specific and potent inhibitory activity on PGE2-mediated pro-tumor myeloid cell differentiation and activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919581/antitumor-response-to-a-codon-optimized-hpv-16-e7-hsp70-fusion-antigen-dna-vaccine
#5
Hoorieh Soleimanjahi, Hadi Razavinikoo, Fatemeh Fotouhi, Abdollah Ardebili
BACKGROUND: Vaccines based on virus-like particles are effective against Human Papilloma Virus (HPV) infection; however, they have not shown a therapeutic effect against HPV-associated diseases. New immunotherapy strategies based on immune responses against tumor antigens can positively affect the clearance of HPV-associated lesions. OBJECTIVE: To generate two therapeutic fusion DNA vaccines (optimizedE7/mouseHSP70 and wildE7/mouseHSP70) to induce antitumor specific responses in mice models...
September 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28918477/in-vitro-inhibition-of-hiv-1-replication-in-autologous-cd4-t-cells-indicates-viral-containment-by-multifactorial-mechanisms
#6
Ting Tu, Jianbo Zhan, Danlei Mou, Wei Li, Bin Su, Tong Zhang, Tao Li, Ning Li, Hao Wu, Cong Jin, Huabiao Chen
HIV-1-specific cytotoxic T lymphocytes (CTLs) and neutralizing antibodies (NAbs) are present during chronic infection, but the relative contributions of these effector mechanisms to viral containment remain unclear. Here, using an in vitro model involving autologous CD4(+) T cells, primary HIV-1 isolates, HIV-1-specific CTLs, and neutralizing monoclonal antibodies, we show that b12, a potent and broadly neutralizing monoclonal antibody to HIV-1, was able to block viral infection when preincubated with virus prior to infection, but was much less effective than CTLs at limiting virus replication when added to infected cell cultures...
September 15, 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28903036/culturing-ctls-under-hypoxic-conditions-enhances-their-cytolysis-and-improves-their-anti-tumor-function
#7
Yael Gropper, Tali Feferman, Tali Shalit, Tomer-Meir Salame, Ziv Porat, Guy Shakhar
Cytotoxic T lymphocytes (CTLs) used in immunotherapy are typically cultured under atmospheric O2 pressure but encounter hypoxic conditions inside tumors. Activating CTLs under hypoxic conditions has been shown to improve their cytotoxicity in vitro, but the mechanism employed and the implications for immunotherapy remain unknown. We activated and cultured OT-I CD8 T cells at either 1% or 20% O2. Hypoxic CTLs survived, as well as normoxic ones, in vitro but killed OVA-expressing B16 melanoma cells more efficiently...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28898397/genome-wide-dna-methylation-analysis-of-senescence-in-repetitively-infected-memory-ctls-dna-methylation-analysis-of-repetitively-infected-memory-ctls
#8
Jumpei Shosaku
The immune system including antigen-specific CD8 T cells, which are cytotoxic T lymphocytes (CTLs), can acquire the potential of more effective elimination of the pathogen for reinfection. Since memory CTLs could exert protective immunity after the next response, we aimed to elucidate the substantial change of repetitively infected memory CTLs. Currently, DNA methylation status in repetitively infected memory CTLs is still unknown. Therefore, we performed next generation sequencing (NGS) to evaluate methylation status and transcriptional regulation of naive, primary and secondary memory CD8 T cells on the basis of transcription start sites (TSS)...
September 12, 2017: Immunology
https://www.readbyqxmd.com/read/28895362/-cd133-epitope-vaccine-with-gp96-as-adjuvant-elicits-an-antitumor-t-cell-response-against-leukemia
#9
Shuo Wang, Hongxia Fan, Yang Li, Huaguo Zheng, Xin Li, Changfei Li, Lizhao Chen, Ying Ju, Songdong Meng
Cancer stem cells are currently under intensive investigation due to their capabilities for tumor initiation, self-renewal, and resistance to chemotherapy. CD133 is implicated in stemness and the malignancy of tumor cells. Here, we explored heat shock protein gp96 adjuvanted CD133 epitope vaccine against leukemia. We screened and identified three H2-Kd-restricted cytotoxic T lymphocyte (CTL) epitopes derived from CD133, CD133₄₁₉₋₄₂₈, CD133₇₀₂₋₇₁₀ and CD133₇₆₀₋₇₆₉. The immunogenicity and antitumor activity of the epitope vaccine using heat shock protein gp96 as adjuvant were further determined in CD133⁺ leukemia xenograft mice...
June 25, 2017: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/28888957/investigating-toxicity-specific-to-adjuvanted-vaccines
#10
Mineo Matsumoto, Shin-Ichi Komatsu, Takanori Ikeda, Kazuhiro Shimomura, Kazuto Watanabe, Keiji Hirabayadi, Jun-Ichi Sawada, Kazushige Maki, Kazutoshi Shinoda, Osamu Fueki, Hiroshi Onodera
In an attempt to understand the unique toxicity of adjuvanted vaccines, we studied how toxicity develops over time following vaccine administration. In addition to on- and off-target toxicity typically observed with general pharmaceuticals, we observed toxicity associated with both the generation and the broad action of effectors (antibodies and/or cytotoxic T lymphocytes, CTLs). The impact on effector generation appears to be related to local tolerance specific to the adjuvant. The vaccine immune response by effectors serves to demonstrate species relevance as outlined in the recent WHO guideline on the nonclinical evaluation of adjuvanted vaccines...
September 6, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28888577/crispr-knock-out-ctla-4-enhances-the-anti-tumor-activity-of-cytotoxic-t-lymphocytes
#11
Long Shi, Tongyu Meng, Zhilong Zhao, Jinsheng Han, Wei Zhang, Fei Gao, Jianhui Cai
T cell-mediated anti-tumor immunity plays a pivotal role in cancer immune surveillance. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a protein receptor mainly expressed in activated T cells and regulatory T cells. CTLA-4 competes with CD28 for ligand binding and generates inhibitory signals to attenuate T cell activation. The blockade of CTLA-4 mediated immune inhibitory checkpoint has been associated with enhanced anti-tumor immunity. In this study, we use CRISPR-Cas9 system to knock out (KO) CTLA-4 from cytotoxic T lymphocytes (CTLs) and evaluate its effect on the anti-tumor activity of the CTLs...
September 6, 2017: Gene
https://www.readbyqxmd.com/read/28881713/therapeutic-vaccine-to-cure-large-mouse-hepatocellular-carcinomas
#12
Zhen Han, De Yang, Anna Trivett, Joost J Oppenheim
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with limited therapeutic options. Here we report the development of a therapeutic vaccination regimen (shortened as 'TheraVac') consisting of intratumoral delivery of high-mobility group nucleosome-binding protein 1 (HMGN1), R848/resiquimod, and one of the checkpoint inhibitors (e.g. anti-CTLA4, anti-PD-L1, or low dose of Cytoxan). C57BL/6 mice harboring large (approximately 1 cm in diameter) established subcutaneous Hepa1-6 hepatomas were cured by intratumoral injections of TheraVac and became tumor-free long-term survivors...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877912/type-1-interferons-potentiate-human-cd8-t-cell-cytotoxicity-through-a-stat4-and-granzyme-b-dependent-pathway
#13
Brittney N Newby, Todd M Brusko, Baiming Zou, Mark A Atkinson, Michael Clare-Salzler, Clayton E Mathews
Events defining the progression to human type 1 diabetes (T1D) have remained elusive owing to the complex interaction between genetics, the immune system, and the environment. Type 1 Interferons (T1-IFN) are known to be a constituent of the auto-inflammatory milieu within the pancreas of patients with T1D. However, the capacity of IFNα/β to modulate human activated auto-reactive CD8(+) T cell (CTL) responses within the islets of patients with T1D have not been investigated. Here, we engineer human beta cell specific CTLs and demonstrate that T1-IFN augments cytotoxicity by inducing rapid phosphorylation of STAT4, resulting in direct binding at the granzyme B (GZMB) promoter within 2 hours of exposure...
September 6, 2017: Diabetes
https://www.readbyqxmd.com/read/28874554/effects-of-thymic-selection-on-t-cell-recognition-of-foreign-and-tumor-antigenic-peptides
#14
Jason T George, David A Kessler, Herbert Levine
The advent of cancer immunotherapy has generated renewed hope for the treatment of many malignancies by introducing a number of novel strategies that exploit various properties of the immune system. These therapies are based on the idea that cytotoxic T lymphocytes (CTLs) directly recognize and respond to tumor-associated neoantigens (TANs) in much the same way as they would to foreign peptides presented on cell surfaces. To date, however, nearly all attempts to optimize immunotherapeutic strategies have been empirical...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28870910/induction-and-analysis-of-cytotoxic-t-lymphocytes-that-recognize-autologous-oral-squamous-cell-carcinoma
#15
Jun-Ya Okamoto, Akihiro Miyazaki, Jun-Ichi Kobayashi, Sho Miyamoto, Takanori Sasaki, Takayuki Kanaseki, Yoshihiko Hirohashi, Toshihiko Torigoe, Hiroyoshi Hiratsuka
BACKGROUND: It is essential that cytotoxic T-lymphocytes (CTLs) recognize tumor-associated antigens (TAAs) and exhibit antitumor effects in immunological responses for tumor rejection. However, only a few cases with oral squamous cell carcinoma (OSCC) have been studied for these antitumor mechanisms. We established a cancer cell line and autologous CTL pair for identifying TAAs in OSCC, despite difficulties in establishing such a pair. MATERIALS AND METHODS: A cell line (OTM) from a primary lesion and a CTL line (TcOTM) were derived from OSCC in a 64-year-old female patient...
September 2017: Anticancer Research
https://www.readbyqxmd.com/read/28864849/maximal-exercise-increases-mucosal-associated-invariant-t-cell-frequency-and-number-in-healthy-young-men
#16
Erik D Hanson, Eli Danson, Catriona V Nguyen-Robertson, Jackson J Fyfe, Nigel K Stepto, David B Bartlett, Samy Sakkal
PURPOSE: Mucosal associated invariant T (MAIT) cells have properties of the innate and acquired immune systems. While the response to vigorous exercise has been established for most leukocytes, MAIT cells have not been investigated. Therefore, the purpose was to determine if MAIT cell lymphocytosis occurs with acute maximal aerobic exercise and if this response is influenced by exercise duration, cardiovascular fitness, or body composition. METHODS: Twenty healthy young males with moderate fitness levels performed an extended graded exercise test until volitional fatigue...
September 1, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28862699/cxorf48-is-a-potential-therapeutic-target-for-achieving-treatment-free-remission-in-cml-patients
#17
M Matsushita, K Ozawa, T Suzuki, M Nakamura, N Nakano, S Kanchi, D Ichikawa, E Matsuki, M Sakurai, D Karigane, H Kasahara, N Tsukamoto, T Shimizu, T Mori, H Nakajima, S Okamoto, Y Kawakami, Y Hattori
Although the introduction of tyrosine kinase inhibitors (TKIs) has improved overall survival of patients with chronic myeloid leukemia (CML), about half of the patients eventually relapse after cessation of TKIs. In contrast, the remainder of the patients maintain molecular remission without TKIs, indicating that the patients' immune system could control proliferation of TKI-resistant leukemic stem cells (LSCs). However, the precise mechanism of immunity against CML-LSCs is not fully understood. We have identified a novel immune target, CXorf48, expressed in LSCs of CML patients...
September 1, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28844759/a-pegylated-hyaluronic-acid-conjugate-for-targeted-cancer-immunotherapy
#18
Jung Min Shin, Se Jin Oh, Seunglee Kwon, V G Deepagan, Minchang Lee, Seok Ho Song, Hyo-Jung Lee, Suyeon Kim, Kwon-Ho Song, Tae Woo Kim, Jae Hyung Park
The cell-free approach to foreignizing tumor cells with non-self antigens has received increasing attention as a method to induce cytotoxic T lymphocyte (CTL)-mediated immunological rejection of tumors, because the clinical translation of the conventional CTL-based cancer immunotherapies has been limited by a complicated manufacturing process and autotransplantation. In this study, we prepared matrix metalloproteinase 9 (MMP9)-responsive polymeric conjugates consisting of PEGylated hyaluronic acid (HA) as the targeting moiety and ovalbumin (OVA) as the model foreign antigen...
August 24, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28839507/comparison-of-immune-responses-in-pigs-infected-with-chinese-highly-pathogenic-prrs-virus-strain-hv-and-north-american-strain-nadc-20
#19
X Li, A Galliher-Beckley, L Wang, J Nietfeld, W Feng, J Shi
INTRODUCTION: Chinese HP-PRRSV characterized by high morbidity and mortality of all ages of pigs emerged since 2006 in China. The immune response of HP-PRRSV was never compared with conventional low pathogenic PRRSV strain. OBJECTIVE: In this study, we compared the immune responses elicited by a Chinese HP-PRRSV strain HV and a North American RRSV strain NADC20 infections. RESULT: Pigs infected with NADC-20 showed significantly higher Ab titers than HV-PRRSV infected pigs at 9 DPI...
2017: Open Virology Journal
https://www.readbyqxmd.com/read/28828008/mesenchymal-stem-cells-attenuate-cisplatin-induced-nephrotoxicity-in-inos-dependent-manner
#20
Bojana Simovic Markovic, Marina Gazdic, Aleksandar Arsenijevic, Nemanja Jovicic, Jovana Jeremic, Valentin Djonov, Nebojsa Arsenijevic, Miodrag L Lukic, Vladislav Volarevic
Mesenchymal stem cells (MSCs) are, due to their immunomodulatory characteristics, utilized in therapy of immune-mediated diseases. We used murine model of cisplatin nephrotoxicity to explore the effects of MSCs on immune cells involved in the pathogenesis of this disease. Intraperitoneal application of MSCs significantly attenuated cisplatin nephrotoxicity, decreased inflammatory cytokines TNF-α and IL-17, and increased anti-inflammatory IL-10, IL-6, nitric oxide (NO), and kynurenine in sera of cisplatin-treated mice...
2017: Stem Cells International
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