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Cytotoxic t lymphocytes

Iêda Maria Martinez Paino, Fabrício Santos, Valtencir Zucolotto
Graphene Oxide (GO) has received enormous attention regarding its possible applications in medical areas including cancer treatment. Nevertheless, graphene biocompatibility and its interactions with cancer, normal and immune system cells still remain a major issue. In the current study, we focused on the immunological impact of GO in the oxidative burst by GO produced in fresh isolated primary human neutrophils, the most abundant leukocyte of immune system. We also studied the GO cytotoxicity, cell uptake and genotoxicity in fresh isolated primary human monocyte, neutrophil, human carcinoma cervical (HeLa) and L929 cells...
October 22, 2016: Journal of Biomedical Materials Research. Part A
Junsik Park, Minsuk Kwon, Eui-Cheol Shin
During immune responses antigen-specific T cells are regulated by several mechanisms, including through inhibitory receptors and regulatory T cells, to avoid excessive or persistent immune responses. These regulatory mechanisms, which are called 'immune checkpoints', suppress T cell responses, particularly in patients with chronic viral infections and cancer where viral antigens or tumor antigens persist for a long time and contribute to T cell exhaustion. Among these regulatory mechanisms, cytotoxic T lymphocyte associated protein-4 (CTLA-4) and programmed cell death 1 (PD-1) are the most well-known receptors and both have been targeted for drug development...
October 21, 2016: Archives of Pharmacal Research
Marek Sierzega, Marzena Lenart, Magdalena Rutkowska, Marta Surman, Bozenna Mytar, Andrzej Matyja, Maciej Siedlar, Jan Kulig
BACKGROUND: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) may serve as a simple index of the immune function. The aim of this study was to investigate the prognostic significance of NLR, PLR, and LMR in patients with resectable pancreatic ductal adenocarcinoma (PDAC) and to verify whether such biomarkers are associated with changes in populations of lymphoid cells. METHODS: The prognostic implications of blood count parameters were evaluated in a retrospective cohort of 442 subjects undergoing pancreatic resections for PDAC...
October 21, 2016: Annals of Surgical Oncology
C Franklin, E Livingstone, A Roesch, B Schilling, D Schadendorf
Malignant melanoma contributes the majority of skin cancer related deaths and shows an increasing incidence in the past years. Despite all efforts of early diagnosis, metastatic melanoma still has a poor prognosis and remains a challenge for treating physicians. In recent years, improved knowledge of the pathophysiology and a better understanding of the role of the immune system in tumour control have led to the development and approval of several immunotherapies. Monoclonal antibodies against different immune checkpoints have been revolutionizing the treatment of metastatic and unresectable melanoma...
September 2, 2016: European Journal of Surgical Oncology
Eiji Matsuura, Yoshimi Enose-Akahata, Karen Yao, Unsong Oh, Yuetsu Tanaka, Hiroshi Takashima, Steven Jacobson
Pathology of HTLV-1 associated myelopathy/Tropical spastic paraparesis (HAM/TSP) is believed to be the result of "bystander damage" involving effector CD8 (+) T lymphocytes (CTLs) killing of virus infected cells. But the specific cellular events leading up to tissue injury are still unclear. Here, we developed the Microscopy Imaging of Cytotoxic T lymphocyte assay with Fluorescence emission (MI-CaFé), an optimized visualization analysis to explore the interactions between CTLs and virus infected or viral antigen presenting target cells...
October 3, 2016: Journal of Neuroimmunology
Greg Hodge, Eugene Roscioli, Hubertus Jersmann, Hai B Tran, Mark Holmes, Paul N Reynolds, Sandra Hodge
BACKGROUND: Corticosteroid resistance is a major barrier to effective treatment of COPD. We have shown that the resistance is associated with decreased expression of glucocorticoid receptor (GCR) by senescent CD28nullCD8+ pro-inflammatory lymphocytes in peripheral blood of COPD patients. GCR must be bound to molecular chaperones heat shock proteins (Hsp) 70 and Hsp90 to acquire a high-affinity steroid binding conformation, and traffic to the nucleus. We hypothesized a loss of Hsp70/90 from these lymphocytes may further contribute to steroid resistance in COPD...
October 21, 2016: Respiratory Research
Nitin Chakravarti, Doina Ivan, Van A Trinh, Isabella C Glitza, Jonathan L Curry, Carlos Torres-Cabala, Michael T Tetzlaff, Roland L Bassett, Victor G Prieto, Wen-Jen Hwu
Ipilimumab, a fully human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), is the first immune checkpoint inhibitor approved for the treatment of unresectable melanoma on the basis of its overall survival (OS) benefit. However, ipilimumab is associated with significant immune-related adverse events. We hypothesized that biomarker exploration of pretreatment tumor samples and correlation with clinical outcome would enable patient selection with an increased benefit/risk ratio for ipilimumab therapy...
October 20, 2016: Melanoma Research
Ashton A Connor, Robert E Denroche, Gun Ho Jang, Lee Timms, Sangeetha N Kalimuthu, Iris Selander, Treasa McPherson, Gavin W Wilson, Michelle A Chan-Seng-Yue, Ivan Borozan, Vincent Ferretti, Robert C Grant, Ilinca M Lungu, Eithne Costello, William Greenhalf, Daniel Palmer, Paula Ghaneh, John P Neoptolemos, Markus Buchler, Gloria Petersen, Sarah Thayer, Michael A Hollingsworth, Alana Sherker, Daniel Durocher, Neesha Dhani, David Hedley, Stefano Serra, Aaron Pollett, Michael H A Roehrl, Prashant Bavi, John M S Bartlett, Sean Cleary, Julie M Wilson, Ludmil B Alexandrov, Malcolm Moore, Bradly G Wouters, John D McPherson, Faiyaz Notta, Lincoln D Stein, Steven Gallinger
Importance: Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. Objective: To classify PDAC according to distinct mutational processes, and explore their clinical significance. Design, Setting, and Participants: We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium...
October 20, 2016: JAMA Oncology
Hengfei Shi, Ke Ren, Baojie Lv, Wei Zhang, Ying Zhao, Ren Xiang Tan, Erguang Li
The roots of Scutellaria baicalensis has been used as a remedy for inflammatory and infective diseases for thousands of years. We evaluated the antiviral activity against respiratory syncytial virus (RSV) infection, the leading cause of childhood infection and hospitalization. By fractionation and chromatographic analysis, we determined that baicalin was responsible for the antiviral activity of S. baicalensis against RSV infection. The concentration for 50% inhibition (IC50) of RSV infection was determined at 19...
October 21, 2016: Scientific Reports
Qian Chen, Ligeng Xu, Chao Liang, Chao Wang, Rui Peng, Zhuang Liu
A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions...
October 21, 2016: Nature Communications
Emilia Pachulec, Vanessa Neitzke-Montinelli, João P B Viola
Nuclear factor of activated T cells (NFAT) 2 null mutant mice die in utero of cardiac failure, precluding analysis of the role of NFAT2 in lymphocyte responses. Only the NFAT2(-/-)/Rag-1(-/-) chimeric mice model gave insight into the role of NFAT2 transcription factor in T lymphocyte development, activation, and differentiation. As reports are mainly focused on the role of NFAT2 in CD4(+) T lymphocytes activation and differentiation, we decided to investigate NFAT2's impact on CD8(+) T lymphocyte responses...
2016: Frontiers in Immunology
Navnit Kumar Mishra, Anil Kumar Sharma, Tapan Kumar Mukherjee
Melanoma is a cancer associated with melanocytes of epidermis. There has been a consistent increase in the number of melanoma patients because of the depletion of the ozone layer which makes it of paramount importance to explore the immunogenic potential of various peptides in melanoma therapy. In the current study, a mutated decapeptide (ELAGIGILTV) epitope ID 12941 was taken from the melanoma antigen recognized by T-cells. This epitope displayed relatively better affinity for histocompatibility leukocyte antigen influencing the proliferation of cytotoxic T-cells...
November 2016: Journal of Molecular Modeling
Uhi Toh, Shuko Saku, Mina Okabe, Nobutaka Iwakuma, Yuko Kimitsuki, Momoko Akashi, Etsuyo Ogo, Akira Yamada, Shigeki Shichijo, Kyogo Itoh, Yoshito Akagi
Our previous phase II clinical trial showed that therapeutically selected personalized peptide vaccines(PPVs)were effective at boosting anticancer immunity; the immune response after PPV was associated with a clinical outcome as a prognostic factor for metastatic breast cancer(mBC). We conducted an early phase II study to evaluate the safety and efficacy of a new regimen using multiple peptide vaccines(KRM-19)for patients with metastatictriple -negative breast cancer. KRM-19 consisted of 19 mixed peptides chosen from the previously reported 31 PPVs according to their anti-tumor immunologiceffec ts and safety profiles for patients with mBC...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Firas El Chaer, Dimpy P Shah, Roy F Chemaly
Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. With prolonged and repeated use of these drugs, CMV can become resistant to standard therapy, resulting in increased morbidity and mortality, especially in HCT recipients. Antiviral drug resistance should be suspected when CMV viremia (DNAemia or antigenemia) fails to improve or continue to increase after 2 weeks of appropriately dosed and delivered antiviral therapy...
October 19, 2016: Blood
Shouzheng Wang, Junling Li
In recent years, squamous non-small cell lung cancer (NSCLC) didn't progress much in chemotherapy or target therapy. However, immunotherapy has made breakthroughs in treating squamous NSCLC. Immunotherapy includes two main broad classes of immune checkpoint inhibitors and therapeutic vaccines. Immune checkpoint inhibitors, including anti cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and anti programmed death receptor 1 (PD-1) antibodies, have been tested in the phase II/III clinical trials and have demonstrated promising outcomes...
October 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
G Chistyakova, I Gazieva, I Remizova, L Ustyantseva, V Lyapunov, S Bychkova
We conducted a study of markers of endothelial dysfunction and angiogenesis regulation, as well as the identification of the main lymphocyte populations, activated CD3 (+) CD95(+)-cells and cytokine-producing CD4 (+) IFN-γ(+)-, CD4 (+) IL-4(+ )-lymphocytes in the 1st trimester of gestation in women with ART-induced pregnancy and spontaneous pregnancy. We used the same indicators to assess the immune status of ELBW infants at birth and at the post-conceptual age of 38-40 weeks. It was determined that the risk factors of very early preterm delivery are: threatened miscarriage, chronic placental insufficiency, endothelial dysfunction, increased spontaneous production of intracellular cytokines...
October 2016: Gynecological Endocrinology
Wataru Obara, Takashi Karashima, Kazuyoshi Takeda, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Keiji Inoue, Toyomasa Katagiri, Taro Shuin, Yusuke Nakamura, Tomoaki Fujioka
PURPOSE: Through genome-wide expression profile analysis, hypoxia-inducible protein 2 (HIG2) has previously been identified as an oncoprotein involved in development/progression of renal cell carcinoma (RCC). We subsequently identified a highly immunogenic HLA-A*0201/0206-restricted epitope peptide (HIG2-9-4) corresponding to a part of HIG2 and applied it as a therapeutic vaccine. We conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC. MATERIALS AND METHODS: Nine patients having HLA-A*0201 or HLA-A*0206 with metastatic or unresectable RCC after failure of the cytokine and/or tyrosine kinase inhibitor therapies were enrolled in this study...
October 18, 2016: Cancer Immunology, Immunotherapy: CII
Maulik Vyas, Ann-Charlott Schneider, Olga Shatnyeva, Katrin S Reiners, Samir Tawadros, Stephan Kloess, Ulrike Köhl, Michael Hallek, Hinrich P Hansen, Elke Pogge von Strandmann
Chronic lymphocytic leukemia (CLL) is the most common form of leukemia that affects B lymphocytes in adults. Natural killer (NK) cells in CLL patients are intrinsically potent but display poor in situ effector functions. NKG2D is an activating receptor found on NK and CD8(+) T cells and plays a role in immunosurveillance of CLL. In this study, we developed mono- and dual-targeting triplebodies utilizing a natural ligand for human NKG2D receptor (ULBP2) to retarget NK cells against tumor cells. Triplebodies in both formats showed better ability to induce NK-cell-dependent killing of target cells compared to bispecific counterparts...
2016: Oncoimmunology
Qiong Liu, Wen Wen, Liang Tang, Chen-Jie Qin, Yan Lin, Hui-Lu Zhang, Han Wu, Charles Ashton, Hong-Ping Wu, Jin Ding, Wei Dong, Le-Xing Yu, Wen Yang, Dan-Dan Huang, Meng-Chao Wu, Hong-Yang Wang, He-Xin Yan
Despite their central function in tumor immunity, dendritic cells (DCs) can respond to inhibitory signals and become tolerogenic, curtailing T cell responses in vivo. Here, we provide the evidence for an inhibitory function of signal regulatory protein (SIRP) α in DC survival and activation. In tumors from human liver cancer patients, infiltrative DCs expressed elevated levels of SIRPα, which is correlated with the induction of immune tolerance within the tumors. Silencing of SIRPα resulted in a significant increase in the longevity of antigen-pulsed DCs in the draining lymph nodes...
2016: Oncoimmunology
Xuhao Zhang, Shan Zhu, Tete Li, Yong-Jun Liu, Wei Chen, Jingtao Chen
Malignant glioma is the most common and a highly aggressive cancer in the central nervous system (CNS). Cancer immunotherapy, strategies to boost the body's anti-cancer immune responses instead of directly targeting tumor cells, recently achieved great success in treating several human solid tumors. Although once considered "immune privileged" and devoid of normal immunological functions, CNS is now considered a promising target for cancer immunotherapy, featuring the recent progresses in neurobiology and neuroimmunology and a highly immunosuppressive state in malignant glioma...
October 16, 2016: Oncotarget
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