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https://www.readbyqxmd.com/read/28924369/il-12-influence-mtor-to-modulate-cd8-t-cells-differentiation-through-t-bet-and-eomesodermin-in-response-to-invasive-pulmonary-aspergillosis
#1
Hao Wang, Jingdong Li, Qiyang Han, Fei Yang, Yu Xiao, Meng Xiao, Yingchun Xu, Longxiang Su, Na Cui, Dawei Liu
Objective: To investigate whether mTOR signaling pathway regulate the proliferation and differentiation of CD8(+) T cells by transcription factors T-bet and Eomes, and explore the role of IL-12 in this biological procedure. Methods: Aspergillus fumigatus spore suspension nasal inhalation was used to establish the invasive pulmonary aspergillosis (IPA) mouse model. After inoculation, rapamycin (2mg/kg) each day or IL-12 (5ug/kg) every other day was given for 7 days. The blood samples were obtained before the mice sacrificed and lung specimens were taken...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28924019/kinetics-and-biomarkers-of-severe-cytokine-release-syndrome-after-cd19-chimeric-antigen-receptor-modified-t-cell-therapy
#2
Kevin A Hay, Laïla-Aïcha Hanafi, Daniel Li, Juliane Gust, W Conrad Liles, Mark M Wurfel, José A López, Junmei Chen, Dominic Chung, Susanna Harju-Baker, Sindhu Cherian, Xueyan Chen, Stanley R Riddell, David G Maloney, Cameron J Turtle
Lymphodepletion chemotherapy followed by infusion of CD19-specific chimeric antigen receptor-modified T cells (CAR-T) has produced impressive antitumor responses in patients with refractory CD19(+) B cell malignancies, but is often associated with cytokine release syndrome (CRS). Our understanding of CRS continues to evolve, and identification of the kinetics of CRS and predictive clinical and laboratory biomarkers of severity are needed to evaluate strategies to mitigate toxicity. We report the clinical presentation and identify biomarkers of severe CRS in 133 adult patients who received CD19 CAR-T cells...
September 18, 2017: Blood
https://www.readbyqxmd.com/read/28920005/the-frequency-of-neoantigens-per-somatic-mutation-rather-than-overall-mutational-load-or-number-of-predicted-neoantigens-per-se-is-a-prognostic-factor-in-ovarian-clear-cell-carcinoma
#3
Hirokazu Matsushita, Kosei Hasegawa, Katsutoshi Oda, Shogo Yamamoto, Akira Nishijima, Yuichi Imai, Kayo Asada, Yuji Ikeda, Takahiro Karasaki, Keiichi Fujiwara, Hiroyuki Aburatani, Kazuhiro Kakimi
Neoantigens derived from tumor-specific somatic mutations are excellent targets for anti-tumor immune responses. In ovarian clear cell carcinoma (OCCC), checkpoint blockade yields durable responses in a subset of patients. To approach the question of why only some patients respond, we first investigated neoantigen loads and immune signatures using exome sequencing and expression array data for 74 OCCC patients treated conventionally. Neither the number of missense mutations nor total predicted neoantigens assessed in the tumor correlated with clinical outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919997/increased-infiltration-and-tolerised-antigen-specific-cd8-tem-cells-in-tumor-but-not-peripheral-blood-have-no-impact-on-survival-of-hcmv-glioblastoma-patients
#4
M Bahador, A Gras Navarro, M A Rahman, M Dominguez-Valentin, S Sarowar, E Ulvestad, G Njølstad, S A Lie, E K Kristoffersen, E Bratland, M Chekenya
Human cytomegalovirus (HCMV) antigens in glioblastoma (GBM) present opportunities for personalised immunotherapy. However, their presence in GBM tissue is still under debate, and evidence of their impact on functional immune responses and prognosis is sparse. Here, we investigated the presence of pp65 (UL83) and immediate early 1 (IE-1) HCMV antigens in a cohort of Norwegian GBM patients (n = 177), using qPCR, immunohistochemistry, and serology. HCMV status was then used to investigate whether viral antigens influenced immune cell phenotype, infiltration, activation and patient survival...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28918040/codon-optimized-p1a-encoding-dna-vaccine-toward-a-therapeutic-vaccination-against-p815-mastocytoma
#5
Alessandra Lopes, Kevin Vanvarenberg, Véronique Préat, Gaëlle Vandermeulen
DNA vaccine can be modified to increase protein production and modulate immune response. To enhance the efficiency of a P815 mastocytoma DNA vaccine, the P1A gene sequence was optimized by substituting specific codons with synonymous ones while modulating the number of CpG motifs. The P815A murine antigen production was increased with codon-optimized plasmids. The number of CpG motifs within the P1A gene sequence modulated the immunogenicity by inducing a local increase in the cytokines involved in innate immunity...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28916780/preserved-immune-functionality-and-high-cmv-specific-t-cell-responses-in-hiv-infected-individuals-with-poor-cd4-t-cell-immune-recovery
#6
Elisabet Gómez-Mora, Elisabet García, Victor Urrea, Marta Massanella, Jordi Puig, Eugenia Negredo, Bonaventura Clotet, Julià Blanco, Cecilia Cabrera
Poor CD4(+) T-cell recovery after cART has been associated with skewed T-cell maturation, inflammation and immunosenescence; however, T-cell functionality in those individuals has not been fully characterized. In the present study, we assessed T-cell function by assessing cytokine production after polyclonal, CMV and HIV stimulations of T-cells from ART-suppressed HIV-infected individuals with CD4(+) T-cell counts >350 cells/μL (immunoconcordants) or <350 cells/μL (immunodiscordants). A group of HIV-uninfected individuals were also included as controls...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28915554/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#7
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912605/peripheral-human-cd4-cd8-t-lymphocytes-exhibit-a-memory-phenotype-and-enhanced-responses-to-il-2-il-7-and-il-15
#8
Marie-Laure Clénet, François Gagnon, Ana Carmena Moratalla, Emilie C Viel, Nathalie Arbour
CD4(+)CD8(+) T lymphocytes account for 1-2% of circulating human T lymphocytes, but their frequency is augmented in several diseases. The phenotypic and functional properties of these T lymphocytes are still ill-defined. We performed an ex vivo characterization of CD4(+)CD8(+) T lymphocytes from the blood of healthy individuals. We observed that CD4(+)CD8(+) T lymphocytes exhibit several characteristics associated with memory T lymphocytes including the expression of chemokine receptors (e.g. CCR7, CXCR3, CCR6) and activation markers (e...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912369/customized-viral-immunotherapy-for-hpv-associated-cancer
#9
Matthew J Atherton, Kyle B Stephenson, Jonathan Pol, Fuan Wang, Charles Lefebvre, David F Stojdl, Jake K Nikota, Anna Dvorkin-Gheva, Andrew Nguyen, Lan Chen, Stephanie Johnson-Obaseki, Patrick J Villeneuve, Jean-Simon Diallo, Jim Dimitroulakos, Yonghong Wan, Brian D Lichty
The viral transforming proteins E6 and E7 make human papilloma virus positive (HPV+) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multi-functional CD8+ T-cell responses...
September 14, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28910403/polymicrobial-sepsis-impairs-bystander-recruitment-of-effector-cells-to-infected-skin-despite-optimal-sensing-and-alarming-function-of-skin-resident-memory-cd8-t-cells
#10
Derek B Danahy, Scott M Anthony, Isaac J Jensen, Stacey M Hartwig, Qiang Shan, Hai-Hui Xue, John T Harty, Thomas S Griffith, Vladimir P Badovinac
Sepsis is a systemic infection that enhances host vulnerability to secondary infections normally controlled by T cells. Using CLP sepsis model, we observed that sepsis induces apoptosis of circulating memory CD8 T-cells (TCIRCM) and diminishes their effector functions, leading to impaired CD8 T-cell mediated protection to systemic pathogen re-infection. In the context of localized re-infections, tissue resident memory CD8 T-cells (TRM) provide robust protection in a variety of infectious models. TRM rapidly 'sense' infection in non-lymphoid tissues and 'alarm' the host by enhancing immune cell recruitment to the site of the infection to accelerate pathogen clearance...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28904691/il-21-augments-rapamycin-in-expansion-of-alpha-fetoprotein-antigen-specific-stem-cell-like-memory-t-cells-in-vitro
#11
Victor Tunje Jeza, Xiaoyi Li, Jun Chen, Zhihui Liang, Adem Onago Aggrey, Xiongwen Wu
INTRODUCTION: Alloreactive tumor specific T cells are important arsenals of the adaptive immune system in the fight against tumors. However, stem cell-like memory T cells (Tscm) provide the key to effective elimination of tumor cells. Methods for generating these T cell subsets already exist. However, they could be made more efficient. Further, they are expensive and unattainable to the resource poor laboratories. In this regard, we are hereby describing a novel in vitro allogeneic co-culture method for raising allo-restricted tumor specific Tscm cells that we developed...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28904110/the-chromatin-accessibility-signature-of-human-immune-aging-stems-from-cd8-t-cells
#12
Duygu Ucar, Eladio J Márquez, Cheng-Han Chung, Radu Marches, Robert J Rossi, Asli Uyar, Te-Chia Wu, Joshy George, Michael L Stitzel, A Karolina Palucka, George A Kuchel, Jacques Banchereau
Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programs behind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptome in PBMCs and purified monocytes, B cells, and T cells. Analysis of samples from 77 young and elderly donors revealed a novel and robust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites...
September 13, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28903041/mir-150-mediated-foxo1-regulation-programs-cd8-t-cell-differentiation
#13
Young Ho Ban, Se-Chan Oh, Sang-Hwan Seo, Seok-Min Kim, In-Pyo Choi, Philip D Greenberg, Jun Chang, Tae-Don Kim, Sang-Jun Ha
MicroRNA (miR)-150 is a developmental regulator of several immune-cell types, but its role in CD8(+) T cells is largely unexplored. Here, we show that miR-150 regulates the generation of memory CD8(+) T cells. After acute virus infection, miR-150 knockout (KO) mice exhibited an accelerated differentiation of CD8(+) T cells into memory cells and improved production of effector cytokines. Additionally, miR-150 KO CD8(+) T cells displayed an enhanced recall response and improved protection against infections with another virus and bacteria...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28903040/mir-150-regulates-memory-cd8%C3%A2-t-cell-differentiation-via-c-myb
#14
Zeyu Chen, Erietta Stelekati, Makoto Kurachi, Sixiang Yu, Zhangying Cai, Sasikanth Manne, Omar Khan, Xiaolu Yang, E John Wherry
MicroRNAs play an important role in T cell responses. However, how microRNAs regulate CD8 T cell memory remains poorly defined. Here, we found that miR-150 negatively regulates CD8 T cell memory in vivo. Genetic deletion of miR-150 disrupted the balance between memory precursor and terminal effector CD8 T cells following acute viral infection. Moreover, miR-150-deficient memory CD8 T cells were more protective upon rechallenge. A key circuit whereby miR-150 repressed memory CD8 T cell development through the transcription factor c-Myb was identified...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28901740/inhibiting-metastasis-and-preventing-tumor-relapse-by-triggering-host-immunity-with-tumor-targeted-photodynamic-therapy-using-photosensitizer-loaded-functional-nanographenes
#15
Xinhe Yu, Duo Gao, Liquan Gao, Jianhao Lai, Chenran Zhang, Yang Zhao, Lijun Zhong, Bing Jia, Fan Wang, Xiaoyuan Chen, Zhaofei Liu
Effective cancer therapy depends not only on destroying the primary tumor but also on conditioning the host immune system to recognize and eliminate residual tumor cells and prevent metastasis. In this study, a tumor integrin αvβ6-targeting peptide (the HK peptide)-functionalized graphene oxide (GO) was coated with a photosensitizer (HPPH). The resulting GO conjugate, GO(HPPH)-PEG-HK, was investigated whether it could destroy primary tumors and boost host antitumor immunity. We found that GO(HPPH)-PEG-HK exhibited significantly higher tumor uptake than GO(HPPH)-PEG and HPPH...
September 18, 2017: ACS Nano
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
#16
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/28894272/t-cell-tolerance-and-exhaustion-in-the-clearance-of-echinococcus-multilocularis-role-of-inoculum-size-in-a-quantitative-hepatic-experimental-model
#17
Chuanshan Zhang, Yingmei Shao, Shuting Yang, Xiaojuan Bi, Liang Li, Hui Wang, Ning Yang, Zhide Li, Cheng Sun, Liang Li, Guodong Lü, Tuerganaili Aji, Dominique A Vuitton, Renyong Lin, Hao Wen
The local immune mechanisms responsible for either self-healing or sustained chronic infection are not clear, in the development of E. multilocularis larvae. Here, we developed a suitable experimental model that mimics naturally infected livers, according to the parasite load. We demonstrated that local cellular immunity and fibrogenesis are actually protective and fully able to limit metacestode growth in the liver of low or medium dose-infected mice (LDG or MDG), or even to clear it, while impairment of cellular immunity is followed by a more rapid and severe course of the disease in high dose-infected mice (HDG)...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28893282/development-of-targeted-adjuvants-for-hiv-1-vaccines
#18
REVIEW
Jun Liu, Mario Ostrowski
Finding new adjuvants is an integrated component of the efforts in developing an effective HIV-1 vaccine. Compared with traditional adjuvants, a modern adjuvant in the context of HIV-1 prevention would elicit a durable and potent memory response from B cells, CD8(+) T cells, and NK cells but avoid overstimulation of HIV-1 susceptible CD4(+) T cells, especially at genital and rectal mucosa, the main portals for HIV-1 transmission. We briefly review recent advances in the studies of such potential targeted adjuvants, focusing on three classes of molecules that we study: TNFSF molecules, TLRs agonists, and NODs agonists...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28888485/immunobiology-of-the-il-15-il-15r%C3%AE-complex-as-an-antitumor-and-antiviral-agent
#19
REVIEW
Yin Guo, Liming Luan, Naeem K Patil, Edward R Sherwood
Interleukin (IL)-15 is essential for natural killer (NK), NKT and memory (m) CD8(+) T cell development and function, and is currently under investigation as an immunotherapeutic agent for the treatment of cancer. Recently, the creation of IL-15 superagonist by complexing IL-15 and its high affinity receptor alpha (IL-15 Rα) in solution, inspired by the natural trans-presentation of IL-15, advances the potential of IL-15-based tumor immunotherapy. IL-15 superagonist shows promising advantages over monomeric IL-15 such as sustaining high circulating concentrations due to prolonged half-life and more potently stimulating NK and CD8(+) T effector lymphocytes...
September 1, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28881482/altered-expression-of-antigen-specific-memory-and-regulatory-t-cell-subsets-differentiate-latent-and-active-tuberculosis
#20
Balaji Pathakumari, Santhi Devasundaram, Alamelu Raja
Though one-third of the world population is infected with M. tuberculosis, only 5-10% of the infected individuals will develop active TB disease and rest will remain infected with no symptoms known as latent TB infection (LTBI). Identifying biomarkers that differentiate latent and active TB disease enables effective TB control, since early detection, treatment of active TB and preventive treatment of LTBI individuals are crucial steps involved in TB control. Here, we have evaluated the frequency of antigen specific memory and regulatory T cells (Tregs) in 15 healthy household contacts (HHC) and 15 pulmonary TB patients (PTB) to identify biomarkers for differential diagnosis of LTBI and active TB...
September 7, 2017: Immunology
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