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Memory t cell cancer

Andrew J Highton, Adam Girardin, Georgia M Bell, Sarah M Hook, Roslyn A Kemp
BACKGROUND: Vaccination generating a robust memory population of CD8(+) T cells may provide protection against cancer. However, immune therapies for cancer are influenced by the local tumour immune microenvironment. An infiltrate of T cells into tumours of people with colorectal cancer has proven to be a significant indicator of good prognosis. METHODS: We used an intracaecal mouse model of cancer to determine whether a protective immune response against a mucosal gut tumour could be generated using a systemic intervention...
October 18, 2016: BMC Immunology
Yang Liu, Srilakshmi Pandeswara, Vinh Dao, Álvaro Padrón, Justin M Drerup, Shunhua Lao, Aijie Liu, Vincent Hurez, Tyler J Curiel
mTOR drives tumor growth but also supports T cell function, rendering the applications of mTOR inhibitors complex especially in T cell malignancies. Here we studied the effects of the mTOR inhibitor rapamycin in mouse EL4 T cell lymphoma. Typical pharmacologic rapamycin (1-8 mg/kg) significantly reduced tumor burden via direct suppression of tumor cell proliferation and improved survival in EL4 challenge independent of anti-tumor immunity. Denileukin diftitox (DD)-mediated depletion of regulatory T cells significantly slowed EL4 growth in vivo in a T cell-dependent fashion...
October 13, 2016: Cancer Research
Y Zhang, C Ma, M Wang, H Hou, L Cui, C Jiang, J Sun, X Qu
BACKGROUND: The role of the interaction between tumor cells and inflammatory cells in gallbladder carcinoma (GBC) is unclear. Inflammatory cells exist in both the tumor immune microenvironment and the host peripheral blood circulatory system. In the current study, we examined the prognostic value of inflammatory cells in the tumor microenvironment and peripheral blood in patients with GBC. METHODS: 98 patients with GBC were recruited in this retrospective study...
October 7, 2016: Clinical & Translational Oncology
Cara C Schafer, Yong Wang, Kenneth P Hough, Anandi Sawant, Stefan C Grant, Victor J Thannickal, Jaroslaw Zmijewski, Selvarangan Ponnazhagan, Jessy S Deshane
Indoleamine 2,3-dioxygenase (IDO) has been implicated in immune evasion by tumors. Upregulation of this tryptophan (Trp)-catabolizing enzyme, in tumor cells and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment (TME), leads to Trp depletion that impairs cytotoxic T cell responses and survival; however, exact mechanisms remain incompletely understood. We previously reported that a combination therapy of gemcitabine and a superoxide dismutase mimetic promotes anti-tumor immunity in a mouse model of lung cancer by inhibiting MDSCs, enhancing polyfunctional response of CD8+ memory T cells, and extending survival...
September 26, 2016: Oncotarget
Stina Syrjänen, Jaana Rautava
HPV-associated head and neck squamous cell carcinoma (HNSCC), more specifically the incidence of oropharyngeal cancer, is dramatically increasing in industrialized countries. According to what has been learned from anogenital vaccination programs, there are reasons to believe that current human papillomavirus (HPV) vaccinations may be potentially effective also against HNSCC. However, before specific results on HNSCC are available, one must keep in mind that carcinogenesis in the head and neck region may differ from that of the anogenital tract...
2017: Recent Results in Cancer Research
María Del Mar Valenzuela-Membrives, Francisco Perea-García, Abel Sanchez-Palencia, Francisco Ruiz-Cabello, Mercedes Gómez-Morales, María Teresa Miranda-León, Inmaculada Galindo-Angel, María Esther Fárez-Vidal
Immune cell infiltration is a common feature of many human solid tumors. Innate and adaptative immune systems contribute to tumor immunosurveillance. We investigated whether tumors evade immune surveillance by inducing states of tolerance and/or through the inability of some immune subpopulations to effectively penetrate tumor nests. Immunohistochemistry and flow cytometry analysis were used to study the composition and distribution of immune subpopulations in samples of peripheral blood, tumor tissue (TT), adjacent tumor tissue (ATT), distant non-tumor tissue (DNTT), cancer nests, cancer stroma, and invasive margin in 61 non-small-cell lung cancer (NSCLC) patients...
September 26, 2016: Oncotarget
Yin Ting Cheung, Noah D Sabin, Wilburn E Reddick, Deepa Bhojwani, Wei Liu, Tara M Brinkman, John O Glass, Scott N Hwang, Deokumar Srivastava, Ching-Hon Pui, Leslie L Robison, Melissa M Hudson, Kevin R Krull
BACKGROUND: Leukoencephalopathy is observed in some children undergoing chemotherapy for acute lymphoblastic leukaemia, although its effects on long-term outcomes is unknown. This study examines the associations between acute leukoencephalopathy and neurobehavioural, neurocognitive, and brain white matter imaging outcomes in long-term survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy without cranial radiation. METHODS: In this longitudinal analysis, we used data of children with acute lymphoblastic leukaemia at St Jude Children's Research Hospital (Memphis, TN, USA) who had been treated between June 1, 2000, and Oct 31, 2010...
October 2016: Lancet Haematology
Fenne L Komdeur, Maartje C A Wouters, Hagma H Workel, Aline M Tijans, Anouk L J Terwindt, Kim L Brunekreeft, Annechien Plat, Harry G Klip, Florine A Eggink, Ninke Leffers, Wijnand Helfrich, Douwe F Samplonius, Edwin Bremer, G Bea A Wisman, Toos Daemen, Evelien W Duiker, Harry Hollema, Hans W Nijman, Marco de Bruyn
CD103+ tumor-infiltrating lymphocytes (TIL) have been linked to specific epithelial infiltration and a prolonged survival in high-grade serous epithelial ovarian cancer (HGSC). However, whether these cells are induced as part of an ongoing anti-HGSC immune response or represent non-specifically expanded resident or mucosal lymphocytes remains largely unknown. In this study, we first confirmed that CD103+ TIL from HGSC were predominantly localized in the cancer epithelium and were strongly correlated with an improved prognosis...
September 16, 2016: Oncotarget
Cesare Gridelli, Paolo A Ascierto, Massimo C P Barberis, Enriqueta Felip, Edward B Garon, Mary O'brien, Suresh Senan, Francesca Casaluce, Assunta Sgambato, Vali Papadimitrakopoulou, Filippo De Marinis
INTRODUCTION: The potential long term survival gain, related to immune adaptability and memory, the potential activity across multiple tumour types through targeting the immune system, and the opportunity for combinations offered by the unique mechanism of actions and safety profile of these new agents, all support the role of immunotherapy in the cancer treatment pathway or paradigm. AREAS COVERED: The authors discuss the recent advances in the understanding of immunology and antitumor immune responses that have led to the development of new immunotherapies, including monoclonal antibodies that inhibit immune checkpoint pathways, such as Programmed Death-1 (PD-1) and Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4)...
September 21, 2016: Expert Opinion on Biological Therapy
Eva Kristine Klemsdal Henriksen, Kristin Kaasen Jørgensen, Fatemeh Kaveh, Kristian Holm, David Hamm, Johanna Olweus, Espen Melum, Brian K Chung, Tor J Eide, Knut E A Lundin, Kirsten Muri Boberg, Tom H Karlsen, Gideon M Hirschfield, Evaggelia Liaskou
BACKGROUND & AIMS: Recruitment of gut-derived memory T cells to the liver is believed to drive hepatic inflammation in primary sclerosing cholangitis (PSC). However, whether gut-infiltrating and liver-infiltrating T cells share T-cell receptors (TCRs) and antigenic specificities is unknown. We used paired gut and liver samples from PSC patients with concurrent inflammatory bowel disease (PSC-IBD), and normal tissue samples from colon cancer controls, to assess potential T-cell clonotype overlap between the two compartments...
September 16, 2016: Journal of Hepatology
Jarushka Naidoo, Xuan Wang, Kaitlin M Woo, Tunc Iyriboz, Darragh Halpenny, Jane Cunningham, Jamie E Chaft, Neil H Segal, Margaret K Callahan, Alexander M Lesokhin, Jonathan Rosenberg, Martin Voss, Charles M Rudin, Hira Rizvi, Xue Hou, Katherine Rodriguez, Melanie Albano, Ruth-Ann Gordon, Charles Leduc, Natasha Rekhtman, Bianca Harris, Alexander M Menzies, Alexander D Guminski, Matteo S Carlino, Benjamin Y Kong, Jedd D Wolchok, Michael A Postow, Georgina V Long, Matthew D Hellmann
PURPOSE: Pneumonitis is an uncommon but potentially fatal toxicity of anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibodies (mAbs). Clinical, radiologic, and pathologic features are poorly described. METHODS: Patients who received anti-PD-1/PD-L1 monotherapy or in combination with anti-cytotoxic T-cell lymphocyte-4 mAb were identified at two institutions (Memorial Sloan Kettering Cancer Center: advanced solid cancers, 2009 to 2014, and Melanoma Institute of Australia: melanomas only, 2013 to 2015)...
September 19, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Rebecca A Evans, Mark S Diamond, Andrew J Rech, Timothy Chao, Max W Richardson, Jeffrey H Lin, David L Bajor, Katelyn T Byrne, Ben Z Stanger, James L Riley, Nune Markosyan, Rafael Winograd, Robert H Vonderheide
In carcinogen-driven cancers, a high mutational burden results in neoepitopes that can be recognized immunologically. Such carcinogen-induced tumors may evade this immune response through "immunoediting," whereby tumors adapt to immune pressure and escape T cell-mediated killing. Many tumors lack a high neoepitope burden, and it remains unclear whether immunoediting occurs in such cases. Here, we evaluated T cell immunity in an autochthonous mouse model of pancreatic cancer and found a low mutational burden, absence of predicted neoepitopes derived from tumor mutations, and resistance to checkpoint immunotherapy...
September 8, 2016: JCI Insight
Troy Z Horvat, Joshua J Pecoraro, Ryan J Daley, Larry W Buie, Amber C King, Raajit K Rampal, Martin S Tallman, Jae H Park, Dan Douer
Asparaginase administration has become a crucial component of front-line pediatric and pediatric-insipired multi-agent regimens for the treatment of acute lymphoblastic leukemia (ALL). The aim of this retrospective study was to assess the safety and feasibility of switching to Erwinia asparaginase after pegaspargase intolerance in adult ALL patients treated at Memorial Sloan Kettering Cancer Center. Our analysis included 10 patients, with a median age of 39 years (range 20-72), male predominance (90%), and a typical B-cell to T-cell ratio (70:30%) for ALL...
August 26, 2016: Leukemia Research
Matthias Braun, Marie L Ress, Young-Eun Yoo, Claus J Scholz, Matthias Eyrich, Paul G Schlegel, Matthias Wölfl
Interleukin 12 (IL12) is a key inflammatory cytokine critically influencing Th1/Tc1-T-cell responses at the time of initial antigen encounter. Therefore, it may be exploited for cancer immunotherapy. Here, we investigated how IL12, and other inflammatory cytokines, shape effector functions of human T-cells. Using a defined culture system, we followed the gradual differentiation and function of antigen-specific CD8(+) T cells from their initial activation as naïve T cells through their expansion phase as early memory cells to full differentiation as clonally expanded effector T cells...
July 2016: Oncoimmunology
Eleftheria A Anastasopoulou, Ioannis F Voutsas, Michael Papamichail, Constantin N Baxevanis, Sonia A Perez
Realizing the basis for generating long-lasting clinical responses in cancer patients after therapeutic vaccinations provides the means to further ameliorate clinical efficacy. Peptide cancer vaccines stimulating CD4(+) T helper cells are often promising for inducing immunological memory and persistent CD8(+) cytotoxic T cell responses. Recent reports from our clinical trial with the AE37 vaccine, which is a HER2 hybrid polypeptide, documented its efficacy to induce CD4(+) T cell immunity, which was associated with clinical improvements preferentially among HLA-DRB1*11(+) prostate cancer patients...
July 2016: Oncoimmunology
Vedran Brezar, Véronique Godot, Liang Cheng, Lishan Su, Yves Lévy, Nabila Seddiki
Efficient vaccines are characterized by the establishment of long-lived memory T cells, including T-helper (effectors and follicular) and T-regulatory cells (Tregs). While the former induces cytotoxic or antibody responses, the latter regulates immune responses by maintaining homeostasis. The role of Tregs in inflammatory conditions is ambiguous and their systematic monitoring in vaccination along with effector T-cells is not instinctive. Recent studies from the cancer field clearly showed that Tregs suppress vaccine-induced immune responses and correlate with poor clinical benefit...
September 5, 2016: Vaccines
Euphemia W Mu, Jesse M Lewin, Mary L Stevenson, Shane A Meehan, John A Carucci, Daniel S Gareau
Importance: Confocal microscopy has the potential to provide rapid bedside pathologic analysis, but clinical adoption has been limited in part by the need for physician retraining to interpret grayscale images. Digitally stained confocal mosaics (DSCMs) mimic the colors of routine histologic specimens and may increase adaptability of this technology. Objective: To evaluate the accuracy and precision of 3 physicians using DSCMs before and after training to detect basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in Mohs micrographic surgery fresh-tissue specimens...
September 7, 2016: JAMA Dermatology
Yuka Kobayashi, Takeshi Watanabe
We previously generated artificial lymph node-like tertiary lymphoid organs (artTLOs) in mice using lymphotoxin α-expressing stromal cells. Here, we show the construction of transplantable and functional artTLOs by applying soluble factors trapped in slow-releasing gels in the absence of lymphoid tissue organizer stromal cells. The resultant artTLOs were easily removable, transplantable, and were capable of attracting memory B and T cells. Importantly, artTLOs induced a powerful antigen-specific secondary immune response, which was particularly pronounced in immune-compromised hosts...
2016: Frontiers in Immunology
Eoin F McKinney, Kenneth G C Smith
During acute viral infection CD8 T cells rapidly expand before contracting down to a persistent memory population that confers long-lasting immunity. However when the antigen persists, such as during chronic viral infection, a dysfunctional process termed 'exhaustion' limits the antiviral response, facilitating ongoing viraemia and poor clinical outcome. CD8 T cell exhaustion was originally identified in lymphocytic choriomeningitis virus (LCMV) infection of mice however new evidence has shown that exhaustion is associated with the control of a wide range of human chronic inflammatory states including chronic viral infection, autoimmunity and cancer...
August 31, 2016: Immunology and Cell Biology
Yang-Zhuo Gu, Chuan-Wen Fan, Ran Lu, Bin Shao, Ya-Xiong Sang, Qiao-Rong Huang, Xue Li, Wen-Tong Meng, Xian-Ming Mo, Yu-Quan Wei
Genetic modification of whole-cell cancer vaccines to augment their efficacies has a history of over two and a half decades. Various genes and gene combinations, targeting different aspects of immune responses have been tested in pursuit of potent adjuvant effects. Here we show that co-expression of two cytokine members of the common cytokine receptor γ-chain family, IL-21 and IL-7, in whole-cell cancer vaccines boosts antitumor immunity in a CD4(+) and CD8(+) T cell-dependent fashion. It also generates effective immune memory...
2016: Scientific Reports
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