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Killer T cells cancer

Chao Liu, Wei Wang, Xiangying Meng, Bing Sun, Yang Cong, Jiannan Liu, Qian Wang, Guangxian Liu, Shikai Wu
Background: Previous studies have demonstrated the prognostic value of globulin (GLB), albumin (ALB), the ALB/GLB ratio (AGR), body mass index (BMI), hemoglobin (Hb), and prognostic nutritional index (PNI) in breast cancer. The underlying mechanism has been investigated by examining the impact of nutritional parameters on T cells, natural killer cells, and dendritic cells, but little is known about their effect on checkpoint molecules. Methods: Here, we investigated the correlation of mRNA expression of programmed cell death protein 1 (PD-1), cluster of differentiation 28 (CD28), cytotoxic T-lymphocyte antigen-4 (CTLA-4), and cluster of differentiation 25 (CD25) with AGR, ALB, GLB, total protein, pre-ALB, Hb, BMI, and PNI in the peripheral blood of breast cancer patients...
2018: OncoTargets and Therapy
Edward Hammond, Nicole M Haynes, Carleen Cullinane, Todd V Brennan, Darryn Bampton, Paul Handley, Tomislav Karoli, Fleur Lanksheer, Liwen Lin, Yiping Yang, Keith Dredge
BACKGROUND: Pixatimod (PG545) is a novel clinical-stage immunomodulatory agent capable of inhibiting the infiltration of tumor-associated macrophages (TAMs) yet also stimulate dendritic cells (DCs), leading to activation of natural killer (NK) cells. Preclinically, pixatimod inhibits heparanase (HPSE) which may be associated with its inhibitory effect on TAMs whereas its immunostimulatory activity on DCs is through the MyD88-dependent TLR9 pathway. Pixatimod recently completed a Phase Ia monotherapy trial in advanced cancer patients...
June 14, 2018: Journal for Immunotherapy of Cancer
Minsung Kim, Suhkneung Pyo, Chung Hyo Kang, Chong Ock Lee, Heung Kyoung Lee, Sang Un Choi, Chi Hoon Park
Gastric cancer is a malignancy that has a high mortality rate. Although progress has been made in the treatment of gastric cancer, many patients experience cancer recurrence and metastasis. Folate receptor 1 (FOLR1) is overexpressed on the cell surface in over one-third of gastric cancer patients, but rarely is expressed in normal tissue. This makes FOLR1 a potential target for chimeric antigen receptor (CAR) T cell immunotherapy, although the function of FOLR1 has not been elucidated. CAR are engineered fusion receptor composed of an antigen recognition region and signaling domains...
2018: PloS One
Éilis Dockry, Seónadh O'Leary, Laura E Gleeson, Judith Lyons, Joseph Keane, Steven G Gray, Derek G Doherty
Immunotherapies that target CD1d-restricted invariant NKT (iNKT) cells can prevent tumor growth in murine models but trials in humans have shown limited clinical efficacy. Here, we show that iNKT cells are depleted from blood and bronchial lavage samples from patients with non-small cell lung cancer (NSCLC) suggesting a role for these cells in immunity against NSCLC. We interrogated the Lung Cancer Explorer and Kaplan-Meier Plotter databases of NSCLC patients and found that pulmonary CD1d expression is reduced in patients with NSCLC and that low expression of CD1d mRNA is significantly associated with poor patient survival...
2018: Oncoimmunology
Ross A Soo, Zhaojin Chen, Rebecca Siew Yan Teng, Hon-Lyn Tan, Barry Iacopetta, Bee Choo Tai, Richie Soong
Background: Tumor-associated immune cells are prognostic in non-small cell lung cancer (NSCLC) but findings have been conflicting. Objectives: To determine the prognostic role of immune cells according to localization in NSCLC patients. Methods: A systematic literature review and meta-analysis was performed on dendritic cell (DC), tumor associated macrophages (TAM), mast cells (MC), natural killer (NK) cells, T and B cells and tumor CTLA-4 and PD-L1 studies...
May 15, 2018: Oncotarget
Clemens Grassberger, Theodore S Hong, Tai Hato, Beow Y Yeap, Jennifer Y Wo, Mark Tracy, Thomas Bortfeld, John A Wolfgang, Christine E Eyler, Lipika Goyal, Jeffrey W Clark, Christopher H Crane, Eugene J Koay, Mark Cobbold, Thomas F DeLaney, Rakesh K Jain, Andrew X Zhu, Dan G Duda
PURPOSE: Irradiation may have significant immunomodulatory effects that impact tumor response and could potentiate immunotherapeutic approaches. The purposes of this study were to prospectively investigate circulating lymphoid cell population fractions during hypofractionated proton therapy (HPT) in blood samples of liver cancer patients and to explore their association with survival. METHODS AND MATERIALS: We collected serial blood samples before treatment and at days 8 and 15 of HPT from 43 patients with liver cancer-22 with hepatocellular carcinoma (HCC) and 21 with intrahepatic cholangiocarcinoma (ICC)-enrolled in a phase 2 clinical trial...
April 17, 2018: International Journal of Radiation Oncology, Biology, Physics
Pablo Mandó, Manglio Rizzo, María Paula Roberti, Estefanía Paula Juliá, María Betina Pampena, Constanza Pérez de la Puente, Carlos Martín Loza, Carolina Ponce, Jorge Nadal, Federico Andres Coló, José Mordoh, Estrella Mariel Levy
Purpose: Breast cancer (BC) is a highly heterogeneous disease presenting a broad range of clinical and molecular characteristics. In the past years, a growing body of evidence demonstrated that immune response plays a significant role in cancer outcome. However, immune prognostic markers are not completely validated in clinical practice in BC patients. Materials and methods: With the aim to characterize immune features, several parameters were analyzed in peripheral blood at diagnosis of 85 nonmetastatic BC patients between April 2011 and July 2014...
2018: OncoTargets and Therapy
Xiaoping Wang, Qiaoxia Wang
Hepatocarcinoma is one of the most prevalent gastroenterological cancers in the world with less effective therapy. As an oncofetal antigen and diagnostic marker for liver cancer, alpha-fetoprotein (AFP) possesses a variety of biological functions. Except for its diagnosis in liver cancer, AFP has become a target for liver cancer immunotherapy. Although the immunogenicity of AFP is weak and it could induce the immune escapes through inhibiting the function of dendritic cells, natural killer cells, and T lymphocytes, AFP has attracted more attention in liver cancer immunotherapy...
2018: Canadian Journal of Gastroenterology & Hepatology
Chi Ma, Miaojun Han, Bernd Heinrich, Qiong Fu, Qianfei Zhang, Milan Sandhu, David Agdashian, Masaki Terabe, Jay A Berzofsky, Valerie Fako, Thomas Ritz, Thomas Longerich, Casey M Theriot, John A McCulloch, Soumen Roy, Wuxing Yuan, Vishal Thovarai, Shurjo K Sen, Mathuros Ruchirawat, Firouzeh Korangy, Xin Wei Wang, Giorgio Trinchieri, Tim F Greten
Primary liver tumors and liver metastasis currently represent the leading cause of cancer-related death. Commensal bacteria are important regulators of antitumor immunity, and although the liver is exposed to gut bacteria, their role in antitumor surveillance of liver tumors is poorly understood. We found that altering commensal gut bacteria in mice induced a liver-selective antitumor effect, with an increase of hepatic CXCR6+ natural killer T (NKT) cells and heightened interferon-γ production upon antigen stimulation...
May 25, 2018: Science
Abner A Murray, Chao Wang, Steven Fiering, Nicole F Steinmetz
Cancer immunotherapy approaches have emerged as novel treatment regimens against cancer. A particularly interesting avenue is the concept of in situ vaccination, where immunostimulatory agents are introduced into an identified tumor to overcome local immunosuppression and, if successful, mount systemic antitumor immunity. We had previously shown that nanoparticles from cowpea mosaic virus (CPMV) are highly potent in inducing long-lasting antitumor immunity when used as an in situ vaccine in various tumor mouse models...
May 25, 2018: Molecular Pharmaceutics
Katharina Fleischhauer, Katharine C Hsu, Bronwen E Shaw
Allogeneic hematopoietic cell transplantation (HCT) is the most established form of cancer immunotherapy and has been successfully applied for the treatment and cure of otherwise lethal neoplastic blood disorders. Cancer immune surveillance is mediated to a large extent by alloreactive T and natural killer (NK) cells recognizing genetic differences between patient and donor. Profound insights into the biology of these effector cells has been obtained over recent years and used for the development of innovative strategies for intelligent donor selection, aiming for improved graft-versus-leukemia effect without unmanageable graft-versus-host disease...
May 24, 2018: Bone Marrow Transplantation
Franco Locatelli, Daniela Pende, Michela Falco, Mariella Della Chiesa, Alessandro Moretta, Lorenzo Moretta
Natural killer (NK) cells are involved in innate defenses against viruses and tumors. Their function is finely tuned by activating and inhibitory receptors. Among the latter, killer immunoglobulin-like receptors and CD94/NKG2A recognize human leukocyte antigen (HLA) Class I molecules, allowing NK cells to discriminate between normal and aberrant cells, as well as to recognize allogeneic cells, because of their ability to sense HLA polymorphisms. This latter phenomenon plays a key role in HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for high-risk acute leukemia patients transplanted from an NK-alloreactive donor...
May 21, 2018: Trends in Immunology
Dhifaf Sarhan, Keli L Hippen, Amanda Lemire, Skyler Hying, Xianghua Luo, Todd Lenvik, Julie Curtsinger, Zachary Davis, Bin Zhang, Sarah Cooley, Frank Cichocki, Bruce R Blazar, Jeffrey S Miller
Natural Killer (NK) cells are capable of fighting viral infections and cancer. However, these responses are inhibited by immune suppressor cells in the tumor microenvironment. Tumor progression promotes the recruitment and generation of intratumoral regulatory T cells (Tregs), associated with a poor prognosis in cancer patients. Here, we show that canonical NK cells are highly susceptible to Treg-mediated suppression, in contrast to highly resistant CD57+ FcεRγ-NKG2C+ adaptive (CD56+CD3-) NK cells that expand in cytomegalovirus (CMV)-exposed individuals...
May 21, 2018: Cancer Immunology Research
Sarah Luu, Elizabeth E Gardiner, Robert K Andrews
The bloodstream typically contains >500 billion anucleate circulating platelets, derived from megakaryocytes in the bone marrow. This review will focus on two interesting aspects of bone marrow dysfunction and how this impacts on the quality of circulating platelets. In this regard, although megakaryocytes are from the myeloid lineage leading to granulocytes (including neutrophils), erythrocytes, and megakaryocytes/platelets, recent evidence has shown that defects in the lymphoid lineage leading to B cells, T cells, and natural killer (NK) cells also result in abnormal circulating platelets...
May 18, 2018: Cancers
Conor J Kearney, Stephin J Vervoort, Simon J Hogg, Kelly M Ramsbottom, Andrew J Freeman, Najoua Lalaoui, Lizzy Pijpers, Jessica Michie, Kristin K Brown, Deborah A Knight, Vivien Sutton, Paul A Beavis, Ilia Voskoboinik, Phil K Darcy, John Silke, Joseph A Trapani, Ricky W Johnstone, Jane Oliaro
Immunotherapy has revolutionized outcomes for cancer patients, but the mechanisms of resistance remain poorly defined. We used a series of whole-genome clustered regularly interspaced short palindromic repeat (CRISPR)-based screens performed in vitro and in vivo to identify mechanisms of tumor immune evasion from cytotoxic lymphocytes [CD8+ T cells and natural killer (NK) cells]. Deletion of key genes within the tumor necrosis factor (TNF) signaling, interferon-γ (IFN-γ) signaling, and antigen presentation pathways provided protection of tumor cells from CD8+ T cell-mediated killing and blunted antitumor immune responses in vivo...
May 18, 2018: Science Immunology
Duane H Hamilton, Kristen K McCampbell, Claudia Palena
The acquisition of mesenchymal features by carcinoma cells is now recognized as a driver of metastasis and tumor resistance to a range of anticancer therapeutics, including chemotherapy, radiation, and certain small-molecule targeted therapies. With the recent successful implementation of immunotherapies for the treatment of various types of cancer, there is growing interest in understanding whether an immunological approach could be effective at eradicating carcinoma cells bearing mesenchymal features. Recent studies, however, demonstrated that carcinoma cells that have acquired mesenchymal features may also exhibit decreased susceptibility to lysis mediated by immune effector cells, including antigen-specific CD8+ T cells, innate natural killer (NK), and lymphokine-activated killer (LAK) cells...
2018: Frontiers in Oncology
Heleen H Van Acker, Diana Campillo-Davo, Gils Roex, Maarten Versteven, Evelien L Smits, Viggo F Van Tendeloo
Cytokines of the common gamma-chain receptor family, comprising interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 and IL-21, are vital with respect to organizing and sustaining healthy immune cell functions. Supporting the anti-cancer immune response, these cytokines inspire great interest for their use as vaccine adjuvants and cancer immunotherapies. It is against this background that gamma delta (γδ) T cells, as special-force soldiers and natural contributors of the tumor immunosurveillance, also received a lot of attention the last decade...
May 14, 2018: Cytokine & Growth Factor Reviews
Qiyue Hu, Xin Ye, Xiangdong Qu, Dongbing Cui, Lei Zhang, Zhibin Xu, Hong Wan, Lianshan Zhang, Weikang Tao
Interleukin-15 (IL-15) can promote both innate and adaptive immune reactions by stimulating CD8+ /CD4+ T cells and natural killer cells (NK) while showing no effect in activating T-regulatory (Treg) cells or inducing activation-associated death among effector T cells and NK cells. Thus, IL-15 is considered as one of the most promising molecules for antitumor immune therapy. To improve the drug-like properties of natural IL-15, we create an IL-15-based molecule, named P22339, with the following characteristics: 1) building a complex of IL-15 and the Sushi domain of IL-15 receptor α chain to enhance the agonist activity of IL-15 via transpresentation; 2) through a rational structure-based design, creating a disulfide bond linking the IL-15/Sushi domain complex with an IgG1 Fc to augment its half-life...
May 16, 2018: Scientific Reports
Rupert Handgretinger, Patrick Schlegel
Recent developments in cell and gene therapy have a great impact on the new therapeutic approaches in pediatric cancers. Monoclonal antibodies for neuroblastoma and bispecific antibodies for leukemia have induced significant clinical responses for otherwise chemorefractory patients. Moreover, cellular therapeutic approaches including chimeric antigen receptor (CAR) T-cells as well as natural killer (NK) cells have the potential to cure patients with so far incurable malignancies and are the basis for future new therapies for pediatric cancer...
April 2018: Chinese Clinical Oncology
Stanislaw Schmidt, Lars Tramsen, Bushra Rais, Evelyn Ullrich, Thomas Lehrnbecher
Natural Killer (NK) cells are involved in the host immune response against infections due to viral, bacterial and fungal pathogens, all of which are a significant cause of morbidity and mortality in immunocompromised patients. Since the recovery of the immune system has a major impact on the outcome of an infectious complication, there is major interest in strengthening the host response in immunocompromised patients, either by using cytokines or growth factors or by adoptive cellular therapies transfusing immune cells such as granulocytes or pathogen-specific T-cells...
April 17, 2018: Oncotarget
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