Read by QxMD icon Read

T cell suppression

Lorraine A O'Reilly, Tracy L Putoczki, Lisa A Mielke, Jun T Low, Ann Lin, Adele Preaudet, Marco J Herold, Kelvin Yaprianto, Lin Tai, Andrew Kueh, Guido Pacini, Richard L Ferrero, Raffi Gugasyan, Yifang Hu, Michael Christie, Stephen Wilcox, Raelene Grumont, Michael D W Griffin, Liam O'Connor, Gordon K Smyth, Mathias Ernst, Paul Waring, Steve Gerondakis, Andreas Strasser
Polymorphisms in NFKB1 that diminish its expression have been linked to human inflammatory diseases and increased risk for epithelial cancers. The underlying mechanisms are unknown, and the link is perplexing given that NF-κB signaling reportedly typically exerts pro-tumorigenic activity. Here we have shown that NF-κB1 deficiency, even loss of a single allele, resulted in spontaneous invasive gastric cancer (GC) in mice that mirrored the histopathological progression of human intestinal-type gastric adenocarcinoma...
March 20, 2018: Immunity
Raul Vizcardo, Nicholas D Klemen, S M Rafiqul Islam, Devikala Gurusamy, Naritaka Tamaoki, Daisuke Yamada, Haruhiko Koseki, Benjamin L Kidder, Zhiya Yu, Li Jia, Amanda N Henning, Meghan L Good, Marta Bosch-Marce, Takuya Maeda, Chengyu Liu, Zied Abdullaev, Svetlana Pack, Douglas C Palmer, David F Stroncek, Fumito Ito, Francis A Flomerfelt, Michael J Kruhlak, Nicholas P Restifo
Induced pluripotent stem cell (iPSC)-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4+ CD8+ double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8αβ+ antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs)...
March 20, 2018: Cell Reports
Sharon Wei Ling Lee, Giulia Adriani, Erica Ceccarello, Andrea Pavesi, Anthony Tanoto Tan, Antonio Bertoletti, Roger Dale Kamm, Siew Cheng Wong
In the hepatitis B virus (HBV)-related hepatocellular carcinoma tumor microenvironment (TME), monocytes reportedly impede natural T cell functions via PD-L1/PD-1 signaling. However, it remains unclear if T cell receptor-redirected T cells (TCR T cells) are similarly inhibited. Hence, we developed a 3D intrahepatic TME microfluidic model to investigate the immunosuppressive potential of monocytes toward HBV-specific TCR T cells and the role of PD-L1/PD-1 signaling. Interestingly, in our 3D static microfluidic model, we observed that monocytes suppressed only retrovirally transduced (Tdx) TCR T cell cytotoxicity toward cancer cells via PD-L1/PD-1, while mRNA electroporated (EP) TCR T cell cytotoxicity was not affected by the presence of monocytes...
2018: Frontiers in Immunology
Jhajaira M Araujo, Andrea C Gomez, Alfredo Aguilar, Roberto Salgado, Justin M Balko, Leny Bravo, Franco Doimi, Denisse Bretel, Zaida Morante, Claudio Flores, Henry L Gomez, Joseph A Pinto
Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with limited options of targeted therapy. Recent findings suggest that the clinical course of TNBC may be modified by the presence of tumor-infiltrating lymphocytes (TILs) and chemokine's expression, such as CCL5. Diverse studies have shown that CCL5 suppresses anti-tumor immunity and it has been related to poor outcome in different types of cancer while in other studies, this gene has been related with a better outcome. We sought to determine the association of CCL5 with the recruitment of TILs and other immune cells...
March 20, 2018: Scientific Reports
Nancy R Stallings, Melissa A O'Neal, Jie Hu, Ege T Kavalali, Ilya Bezprozvanny, James S Malter
Early-stage Alzheimer's disease is characterized by the loss of dendritic spines in the neocortex of the brain. This phenomenon precedes tau pathology, plaque formation, and neurodegeneration and likely contributes to synaptic loss, memory impairment, and behavioral changes in patients. Studies suggest that dendritic spine loss is induced by soluble, multimeric amyloid-β (Aβ42 ), which, through postsynaptic signaling, activates the protein phosphatase calcineurin. We investigated how calcineurin caused spine pathology and found that the cis-trans prolyl isomerase Pin1 was a critical downstream target of Aβ42 -calcineurin signaling...
March 20, 2018: Science Signaling
Sana Hibino, Shunsuke Chikuma, Taisuke Kondo, Minako Ito, Hiroko Nakatsukasa, Setsuko Omata-Mise, Akihiko Yoshimura
Enhanced infiltration of regulatory T (Treg) cells into tumor tissue is detrimental to cancer patients and closely associated with poor prognosis as they create an immunosuppressive state that suppresses anti-tumor immune responses. Therefore, breaking Treg-mediated immune tolerance is important when considering cancer immunotherapy. Here we show that the Nr4a nuclear receptors, key transcription factors maintaining Treg cell genetic programs, contribute to Treg-mediated suppression of anti-tumor immunity in the tumor microenvironment...
March 20, 2018: Cancer Research
Abhinav Saurabh, Sushmita Chakraborty, Prabin Kumar, Anant Mohan, Anuj K Bhatnagar, Narayan Rishi, Dipendra Kumar Mitra
Human Leukocyte Antigen-G (HLA-G), a non-classical, class Ib molecule, has been shown to mediate immunoregulatory functions by inducing apoptosis, inhibits cytotoxicity and differentiation by modulating cytokine secretion. Due to its immune-suppressive function, it facilitates tolerance in feto-maternal interface and transplantation. In contrary, it favours immune evasion of microbes and tumors by inhibiting immune and inflammatory responses. In Tuberculosis (TB), we previously reported differential expression of HLA-G and its receptor Ig-like transcript -2 (ILT-2) in disseminated vs...
March 2018: Tuberculosis
Karin Kfir-Elirachman, Rona Ortenberg, Bella Vizel, Michal J Besser, Iris Barshack, Jacob Schachter, Yael Nemlich, Gal Markel
BRAF becomes constitutively activated in 50% to 70% of melanoma cases. CEACAM1 has a dual role in melanoma, including facilitation of cell proliferation and suppression of infiltrating lymphocytes, which are consistent with its value as a marker for poor prognosis in melanoma patients. Here we show that BRAFV600E melanoma cells treated with BRAF and MEK inhibitors (MAPKi) downregulate CEACAM1 mRNA and protein expression in a dose- and exposure time-dependent manners. Indeed, there is a significant correlation between the presence of BRAFV600E and CEACAM1 expression in melanoma specimens obtained from 45 patients...
March 17, 2018: Neoplasia: An International Journal for Oncology Research
Michael T Tetzlaff, Priyadharsini Nagarajan
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Incidence of MCC continues to rise, and risk factors include advanced age, pale skin, chronic sun exposure, and immune suppression. Diagnosing MCC utilizes a combination of morphology and immunohistochemistry. Merkel cell polyomavirus (MCPyV) is present in approximately 70-80% of MCCs and represents a key pathogenic driver in those MCCs. In contrast, MCPyV-negative MCCs arise through progressive accumulation of ultraviolet-light induced somatic mutations...
March 20, 2018: Head and Neck Pathology
Lu Gan, Yanan Yang, Qian Li, Yi Feng, Tianshu Liu, Weijian Guo
Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and a catalytic component of PRC2, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) to regulate gene expression through epigenetic machinery. EZH2 also functions both as a transcriptional suppressor and a transcriptional co-activator, depending on H3K27me3 or not and on the different cellular contexts. Unsurprisingly, numerous studies have highlighted the role of EZH2 in cancer development and progression. Through modulating critical gene expression, EZH2 promotes cell survival, proliferation, epithelial to mesenchymal, invasion, and drug resistance of cancer cells...
2018: Biomarker Research
Chunhui Lai, Siliang Duan, Fang Ye, Xiaoqiong Hou, Xi Li, Jin Zhao, Xia Yu, Zixi Hu, Zhuoran Tang, Fengzhen Mo, Xiaomei Yang, Xiaoling Lu
PURPOSE: Dendritic cell (DC)-based cancer vaccines is a newly emerging and potent form of immune therapy. As for any new technology, there are still considerable challenges that need to be addressed. Here, we investigate the antitumor potential of a novel liposomal vaccine, M/CpG-ODN-TRP2-Lipo. METHODS: We developed a vaccination strategy by assembling the DC-targeting mannose and immune adjuvant CpG-ODN on the surface of liposomes, which were loaded with melanoma-specific TRP2180-188 peptide as liposomal vaccine...
2018: Theranostics
Jiehua Zhou, Daniel Lazar, Haitang Li, Xin Xia, Sangeetha Satheesan, Paige Charlins, Denis O'Mealy, Ramesh Akkina, Sheena Saayman, Marc S Weinberg, John J Rossi, Kevin V Morris
Gene-based therapies represent a promising therapeutic paradigm for the treatment of HIV-1, as they have the potential to maintain sustained viral inhibition with reduced treatment interventions. Such an option may represent a long-term treatment alternative to highly active antiretroviral therapy. Methods: We previously described a therapeutic approach, referred to as transcriptional gene silencing (TGS), whereby small noncoding RNAs directly inhibit the transcriptional activity of HIV-1 by targeting sites within the viral promoter, specifically the 5' long terminal repeat (LTR)...
2018: Theranostics
Rachel V Jimenez, Tyler T Wright, Nicholas R Jones, Jianming Wu, Andrew W Gibson, Alexander J Szalai
C-reactive protein (CRP) is the prototypical acute phase reactant, increasing in blood concentration rapidly and several-fold in response to inflammation. Recent evidence indicates that CRP has an important physiological role even at low, baseline levels, or in the absence of overt inflammation. For example, we have shown that human CRP inhibits the progression of experimental autoimmune encephalomyelitis (EAE) in CRP transgenic mice by shifting CD4+ T cells away from the TH 1 and toward the TH 2 subset. Notably, this action required the inhibitory Fcγ receptor IIB (FcγRIIB), but did not require high levels of human CRP...
2018: Frontiers in Immunology
Yusheng Cheng, Hui Li, Yinan Deng, Yan Tai, Kaining Zeng, Yingcai Zhang, Wei Liu, Qi Zhang, Yang Yang
Emerging evidence indicate that cancer-associated fibroblasts (CAFs) affect tumor progression by reshaping the tumor microenvironment. Neutrophils are prominent components of solid tumors and important in cancer progression. Whether the phenotype and function of neutrophils in hepatocellular carcinoma (HCC) are influenced by CAFs is not well understood. Herein, we investigated the effect of HCC-derived CAFs (HCC-CAFs) on the neutrophils and explored the biological role of this effect. We found that HCC-CAFs induced chemotaxis of neutrophils and protected them from spontaneous apoptosis...
March 19, 2018: Cell Death & Disease
Yuki Katayama, Masashi Tachibana, Nozomi Kurisu, Yukako Oya, Yuichi Terasawa, Hiroshi Goda, Kouji Kobiyama, Ken J Ishii, Shizuo Akira, Hiroyuki Mizuguchi, Fuminori Sakurai
Oncolytic reovirus, which possesses 10 segments of dsRNA genome, mediates antitumor effects via not only virus replication in a tumor cell-specific manner, but also activation of antitumor immunity; however, the mechanism(s) of reovirus-induced activation of antitumor immunity have not been fully elucidated. Recent studies have demonstrated that overcoming an immunosuppressive environment in tumor-bearing hosts is important to achieve efficient activation of antitumor immunity. Among the various types of cells involved in immunosuppression, it has been revealed that myeloid-derived suppressor cells (MDSCs) are significantly increased in tumor-bearing hosts and play crucial roles in the immunosuppression in tumor-bearing hosts...
March 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Li Huang, Meijuan Wang, Yongdong Yan, Wenjing Gu, Xinxing Zhang, Jiahong Tan, Huiming Sun, Wei Ji, Zhengrong Chen
BACKGROUND: The aim of this study was to investigate the mechanisms of OX40L in regulating helper T (Th) cells differentiation through phosphoinositide 3-kinase (PI3K)/AKT and p38 mitogen-activated protein kinase signaling pathway in vitro and in vivo experiments. METHODS: Serum samples of patients with asthma and healthy controls were used to explore the association between OX40L and Th cells. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum concentrations of OX40L, IL-4, IFN-γ, IL-17 and TGF-β...
March 20, 2018: Journal of Translational Medicine
Henrieta Fraser, Niloufar Safinia, Nathali Grageda, Sarah Thirkell, Katie Lowe, Laura J Fry, Cristiano Scottá, Andrew Hope, Christopher Fisher, Rachel Hilton, David Game, Paul Harden, Andrew Bushell, Kathryn Wood, Robert I Lechler, Giovanna Lombardi
The concept of regulatory T cell (Treg)-based immunotherapy has enormous potential for facilitating tolerance in autoimmunity and transplantation. Clinical translation of Treg cell therapy requires production processes that satisfy the rigors of Good Manufacturing Practice (GMP) standards. In this regard, we report our findings on the implementation of a robust GMP compliant process for the ex vivo expansion of clinical grade Tregs, demonstrating the feasibility of this developed process for the manufacture of a final product for clinical application...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
Tong-Yun Wang, Yong-Gang Liu, Liang Li, Gang Wang, Hai-Ming Wang, Hong-Liang Zhang, Shi-Fei Zhao, Jia-Cong Gao, Tong-Qing An, Zhi-Jun Tian, Yan-Dong Tang, Xue-Hui Cai
Porcine reproductive and respiratory syndrome virus (PRRSV) is a problematic virus that is difficult to control. The principal target cells for PRRSV infection are porcine alveolar macrophages (PAMs). Increasing evidence has demonstrated that CD163 is the determinant receptor for PRRSV infection. However, the relationship between CD163 abundance and PRRSV infection is unclear. In this study, we first generated primary immortalized PAMs (iPAMs) using SV40 large T antigen and demonstrated that CD163 expression is suppressed by the alternative splicing of mRNA in iPAMs...
February 23, 2018: Oncotarget
Li-Yun Fann, Ying Chen, Da-Chen Chu, Shao-Ju Weng, Heng-Cheng Chu, Alexander T H Wu, Jiann-Fong Lee, Ahmed Atef Ahmed Ali, Tsung-Chih Chen, Hsu-Shan Huang, Kuo-Hsing Ma
The small-molecule naphtha [2,3-f]quinoxaline-7,12-dione (NSC745887) can effectively inhibit the proliferation of various cancers by trapping DNA-topoisomerase cleavage. The aim of this study was to elucidate cellular responses of NSC745887 in human glioblastoma multiforme (GBM, U118MG and U87MG cells) and investigate the underlying molecular mechanisms. NSC745887 reduced the cell survival rate and increased the sub-G1 population in dose- and time-dependent manners in GBM cells. Moreover, NSC745887 increased expression of γH2AX and caused DNA fragmentation leading to DNA damage...
February 23, 2018: Oncotarget
Bo Hu, Yuanyuan Ma, Yue Yang, Lijian Zhang, Haibo Han, Jinfeng Chen
Cluster of differentiation 44 (CD44), a marker for cancer stem cells, has been reported to be associated with poor prognosis in non-small cell lung cancer (NSCLC), but its involvement in tumor growth has not fully been elucidated. The present study explored the associations between CD44 expression and clinicopathological features using immunohistochemistry in 94 NSCLC cases, as well as proliferation in cells with aberrant expression of this protein. Overexpression of CD44 was achieved by transfecting H1299 cells with CD44 expression vectors, and inhibition of CD44 expression was performed by transfecting small interfering RNAs into A549 cells...
April 2018: Oncology Letters
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"