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Memory t cell cancer

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https://www.readbyqxmd.com/read/29338031/pre-existing-malignancy-results-in-increased-prevalence-of-distinct-populations-of-cd4-t-cells-during-sepsis
#1
Jianfeng Xie, Jennifer M Robertson, Ching-Wen Chen, Wenxiao Zhang, Craig M Coopersmith, Mandy L Ford
The presence of pre-existing malignancy in murine hosts results in increased immune dysregulation and risk of mortality following a septic insult. Based on the known systemic immunologic changes that occur in cancer hosts, we hypothesized that the presence of pre-existing malignancy would result in phenotypic and functional changes in CD4+ T cell responses following sepsis. In order to conduct a non-biased, unsupervised analysis of phenotypic differences between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor cells and tumors were allowed to grow for 3 weeks...
2018: PloS One
https://www.readbyqxmd.com/read/29331266/human-papilloma-virus-specific-t-cells-can-be-generated-from-na%C3%A3-ve-t-cells-for-use-as-an-immunotherapeutic-strategy-for-immunocompromised-patients
#2
Sarah E McCormack, Conrad Russell Y Cruz, Kaylor E Wright, Allison B Powell, Haili Lang, Cornelia Trimble, Michael D Keller, Ephraim Fuchs, Catherine M Bollard
Human papilloma virus (HPV) is a known cause of cervical cancer, squamous cell carcinoma and laryngeal cancer. Although treatments exist for HPV-associated malignancies, patients unresponsive to these therapies have a poor prognosis. Recent findings from vaccine studies suggest that T-cell immunity is essential for disease control. Because Epstein-Barr Virus (EBV)-specific T cells have been highly successful in treating or preventing EBV-associated tumors, we hypothesized that the development of a manufacturing platform for HPV-specific T cells from healthy donors could be used in a third-party setting to treat patients with high-risk/relapsed HPV-associated cancers...
January 10, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29322091/a-retroviral-replicating-vector-encoding-cytosine-deaminase-and-5-fc-induces-immune-memory-in-metastatic-colorectal-cancer-models
#3
Kader Yagiz, Maria E Rodriguez-Aguirre, Fernando Lopez Espinoza, Tiffany T Montellano, Daniel Mendoza, Leah A Mitchell, Carlos E Ibanez, Noriyuki Kasahara, Harry E Gruber, Douglas J Jolly, Joan M Robbins
Treatment of tumors with Toca 511, a gamma retroviral replicating vector encoding cytosine deaminase, followed by 5-fluorocytosine (5-FC) kills tumors by local production of 5-fluorouracil (5-FU). In brain tumor models, this treatment induces systemic anti-tumor immune responses and long-term immune-mediated survival. Phase 1 Toca 511 and Toca FC (extended-release 5-FC) clinical trials in patients with recurrent high-grade glioma show durable complete responses and promising survival data compared to historic controls...
March 30, 2018: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29319049/mechanisms-of-resistance-to-immune-checkpoint-inhibitors
#4
REVIEW
Russell W Jenkins, David A Barbie, Keith T Flaherty
Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have shown unprecedented clinical activity in several types of cancer and are rapidly transforming the practice of medical oncology. Whereas cytotoxic chemotherapy and small molecule inhibitors ('targeted therapies') largely act on cancer cells directly, immune checkpoint inhibitors reinvigorate anti-tumour immune responses by disrupting co-inhibitory T-cell signalling. While resistance routinely develops in patients treated with conventional cancer therapies and targeted therapies, durable responses suggestive of long-lasting immunologic memory are commonly seen in large subsets of patients treated with ICI...
January 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29316955/single-molecule-techniques-to-quantify-and-genetically-characterise-persistent-hiv
#5
REVIEW
Xiao Qian Wang, Sarah Palmer
Antiretroviral therapy effectively suppresses, but does not eradicate HIV-1 infection. Persistent low-level HIV-1 can still be detected in plasma and cellular reservoirs even after years of effective therapy, and cessation of current treatments invariably results in resumption of viral replication. Efforts to eradicate persistent HIV-1 require a comprehensive examination of the quantity and genetic composition of HIV-1 within the plasma and infected cells located in the peripheral blood and tissues throughout the body...
January 9, 2018: Retrovirology
https://www.readbyqxmd.com/read/29315824/cytokine-secreting-microparticles-engineer-the-fate-and-the-effector-functions-of-t-cells
#6
Fatemeh S Majedi, Mohammad Mahdi Hasani-Sadrabadi, Yoko Kidani, Timothy J Thauland, Alireza Moshaverinia, Manish J Butte, Steven J Bensinger, Louis-S Bouchard
T-cell immunotherapy is a promising approach for cancer, infection, and autoimmune diseases. However, significant challenges hamper its therapeutic potential, including insufficient activation, delivery, and clonal expansion of T-cells into the tumor environment. To facilitate T-cell activation and differentiation in vitro, core-shell microparticles are developed for sustained delivery of cytokines. These particles are enriched by heparin to enable a steady release of interleukin-2 (IL-2), the major T-cell growth factor, over 10+ d...
January 8, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29313971/in-vivo-antitumor-function-of-tumor-antigen-specific-ctls-generated-in-the-presence-of-ox40-co-stimulation-in-vitro
#7
Ngoc Pham Minh, Satoshi Murata, Naomi Kitamura, Tomoyuki Ueki, Masatsugu Kojima, Toru Miyake, Katsushi Takebayashi, Hirokazu Kodama, Eiji Mekata, Masaji Tani
Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8+ T-cells, co-cultured with a tumor specific peptide and a stimulatory anti-OX40 antibody, before being used for ACT therapy in tumor-bearing mouse recipients. Splenic T-cells were obtained from wild-type FVB/N mice that had been injected with a HER2/neu (neu)-expressing tumor and a neu-vaccine...
January 4, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29312597/targeting-of-cd122-enhances-antitumor-immunity-by-altering-the-tumor-immune-environment
#8
Daniel O Villarreal, Michael J Allegrezza, Melissa A Smith, Diana Chin, Leopoldo L Luistro, Linda A Snyder
Mounting evidence demonstrates that CD8+CD122+ T cells have suppressive properties with the capacity to inhibit T cell responses. Therefore, these cells are rational targets for cancer immunotherapy. Here, we demonstrate that CD122 monoclonal antibody (mAb; aCD122) therapy significantly suppressed tumor growth and improved long-term survival in tumor-bearing mice. This therapeutic effect correlated with enhanced polyfunctional, cytolytic intratumoral CD8+ T cells and a decrease in granulocytic myeloid-derived suppressor cells (G-MDSCs)...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311694/intravital-mucosal-imaging-of-cd8-resident-memory-t-cells-shows-tissue-autonomous-recall-responses-that-amplify-secondary-memory
#9
Lalit K Beura, Jason S Mitchell, Emily A Thompson, Jason M Schenkel, Javed Mohammed, Sathi Wijeyesinghe, Raissa Fonseca, Brandon J Burbach, Heather D Hickman, Vaiva Vezys, Brian T Fife, David Masopust
CD8+ T cell immunosurveillance dynamics influence the outcome of intracellular infections and cancer. Here we used two-photon intravital microscopy to visualize the responses of CD8+ resident memory T cells (TRM cells) within the reproductive tracts of live female mice. We found that mucosal TRM cells were highly motile, but paused and underwent in situ division after local antigen challenge. TRM cell reactivation triggered the recruitment of recirculating memory T cells that underwent antigen-independent TRM cell differentiation in situ...
January 8, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29311386/dendritic-cell-based-cancer-vaccines
#10
REVIEW
Patricia M Santos, Lisa H Butterfield
Dendritic cells (DC) are specialized immune cells that play a critical role in promoting an immune response against Ags, which can include foreign pathogenic Ags and self-tumor Ags. DC are capable of boosting a memory T cell response but most importantly they are effective initiators of naive T cell responses. Many years of studies have focused on the use of DC vaccines against cancer to initiate and shape an antitumor-specific immune response and/or boost existing spontaneous antitumor T cell responses. In this study we give a brief overview of DC biology, function, and cellular subsets, and review the current status of the field of DC as cancer vaccines...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29306001/nanoparticulate-vaccine-inhibits-tumor-growth-via-improved-t-cell-recruitment-into-melanoma-and-huher2-breast-cancer
#11
Eva Zupančič, Caterina Curato, Jung-Seok Kim, Eilam Yeini, Ziv Porat, Ana S Viana, Anat Globerson-Levin, Tova Waks, Zelig Eshhar, João N Moreira, Ronit Satchi-Fainaro, Lea Eisenbach, Steffen Jung, Helena F Florindo
Nanoparticulate vaccines are promising tools to overcome cancer immune evasion. However, a deeper understanding on nanoparticle-immune cell interactions and treatments regime are required for optimal efficacy. We provide a comprehensive study of treatment schedules and mode of antigen-association to nanovaccines on the modulation of T cell immunity in vivo, under steady-state and tumor-bearing mice. The coordinated delivery of antigen and two adjuvants (Monophosphoryl lipid A, oligodeoxynucleotide cytosine-phosphate-guanine motifs (CpG)) by nanoparticles was crucial for dendritic cell activation...
January 3, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29305464/resident-memory-t-cells-runx-and-hide
#12
Rachael A Clark
The transcription factor Runx3 enhances the differentiation and survival of CD8+ resident memory T cells; enhancing Runx3 expression in responding T cells could lead to better therapies for infection and cancer.
January 5, 2018: Science Immunology
https://www.readbyqxmd.com/read/29302841/prognostic-value-of-the-glasgow-prognostic-score-for-patients-with-metastatic-renal-cell-carcinoma-treated-by-cytoreductive-nephrectomy
#13
Hironori Fukuda, Toshio Takagi, Tsunenori Kondo, Kazuhiko Yoshida, Satoru Shimizu, Yoji Nagashima, Kazunari Tanabe
BACKGROUND: The aim of the present study was to evaluate the prognostic significance of the Glasgow Prognostic Score (GPS) in metastatic renal cell carcinoma (mRCC) patients treated by cytoreductive nephrectomy (CN), and the accuracy of the GPS as a prognostic factor. METHODS: We retrospectively analyzed the data of patients who underwent CN for mRCC between March 1984 and August 2015. In accordance with the GPS criteria, the patients were classified into three groups: GPS 0: C-reactive protein (CRP) ≤ 1...
January 5, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29295645/favorable-immune-signature-in-cll-patients-defined-by-antigen-specific-t-cell-responses-might-prevent-second-skin-cancers
#14
Juliane Sarah Walz, Daniel Johannes Kowalewski, Linus Backert, Annika Nelde, Oliver Kohlbacher, Benjamin Weide, Lothar Kanz, Helmut Rainer Salih, Hans-Georg Rammensee, Stefan Stevanović
The course of chronic lymphocytic leukemia (CLL), inducing an immunosuppressed state that also affects T cells as central components of adaptive immunity, predisposes patients to develop second malignancies with skin cancer being the most common. Recently, we found that prevalence of memory T cells with specificity for CLL-associated antigens defined by mass spectrometry-based immunopeptidome analysis correlated with a significant survival benefit. Here, we analyzed our CLL patient cohort for second skin (pre)malignancies and found a significantly lower incidence of skin cancer in the patients showing immune responses to CLL-associated antigens...
January 3, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29290787/activity-and-immune-correlates-of-a-programmed-death-1-blockade-antibody-in-the-treatment-of-refractory-solid-tumors
#15
Chang Jiang, Xiuyu Cai, Hongxia Zhang, Xiaojun Xia, Bei Zhang, Liangping Xia
Background: Blockade of programmed death 1 (PD-1), an inhibitory T lymphocyte receptor, is associated with immune system enhancement and tumor remission in various tumors. We assessed the anti-tumor activity and immune correlates of cancer patients treated with an anti-PD-1 antibody. Patients and Methods: Twelve patients with advanced metastatic tumors were treated with anti-PD-1 antibody. Responses were assessed after a 12-week treatment regimen. Biochemical and immunological indexes were measured before each cycle...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29289977/anti-pd-1-induced-high-grade-hepatitis-associated-with-corticosteroid-resistant-t-cells-a-case-report
#16
Helen M McGuire, Elena Shklovskaya, Jarem Edwards, Paul R Trevillian, Geoffrey W McCaughan, Patrick Bertolino, Catriona McKenzie, Ralph Gourlay, Stuart J Gallagher, Barbara Fazekas de St Groth, Peter Hersey
Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control...
December 30, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29285226/parity-improves-anti-tumor-immunity-in-breast-cancer-patients
#17
Anna-Lena Krause, Florian Schuetz, Marc Boudewijns, Maria Pritsch, Markus Wallwiener, Michael Golatta, Joachim Rom, Joerg Heil, Christof Sohn, Andreas Schneeweiss, Philipp Beckhove, Christoph Domschke
Compared to nulliparous women, parous women have an up to 50% lower lifetime risk of developing breast cancer. An endogenous mechanism to prevent the development of cancer is the destruction of tumor cells by T cells that recognize tumor-associated antigens (TAA). Since a number of TAA are also highly present in the breast and placenta of pregnant women, we investigated the induction and characteristics of spontaneous T cell responses against TAA during pregnancy. To this end, we collected peripheral blood from healthy nulliparous, primigravid and parous women, as well as from breast cancer patients...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29284044/long-term-persistence-and-function-of-hematopoietic-stem-cell-derived-chimeric-antigen-receptor-t-cells-in-a-nonhuman-primate-model-of-hiv-aids
#18
Anjie Zhen, Christopher W Peterson, Mayra A Carrillo, Sowmya Somashekar Reddy, Cindy S Youn, Brianna B Lam, Nelson Y Chang, Heather A Martin, Jonathan W Rick, Jennifer Kim, Nick C Neel, Valerie K Rezek, Masakazu Kamata, Irvin S Y Chen, Jerome A Zack, Hans-Peter Kiem, Scott G Kitchen
Chimeric Antigen Receptor (CAR) T-cells have emerged as a powerful immunotherapy for various forms of cancer and show promise in treating HIV-1 infection. However, significant limitations are persistence and whether peripheral T cell-based products can respond to malignant or infected cells that may reappear months or years after treatment remains unclear. Hematopoietic Stem/Progenitor Cells (HSPCs) are capable of long-term engraftment and have the potential to overcome these limitations. Here, we report the use of a protective CD4 chimeric antigen receptor (C46CD4CAR) to redirect HSPC-derived T-cells against simian/human immunodeficiency virus (SHIV) infection in pigtail macaques...
December 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29281850/cd70-encoded-by-modified-vaccinia-virus-ankara-enhances-cd8-t-cell-dependent-protective-immunity-in-mhc-class-ii-deficient-mice
#19
Barbara Bathke, Juliane Pätzold, Ronny Kassub, Raphael Giessel, Kerstin Lämmermann, Maria Hinterberger, Kay Brinkmann, Paul Chaplin, Mark Suter, Hubertus Hochrein, Henning Lauterbach
The immunological outcome of infections and vaccinations is largely determined during the initial first days in which antigen-presenting cells instruct T cells to expand and differentiate into effector and memory cells. Besides the essential stimulation of the T cell receptor complex a plethora of co-stimulatory signals not only ensures a proper T cell activation but also instils phenotypic and functional characteristics in the T cells appropriate to fight off the invading pathogen. The TNF receptor/ligand pair CD27/CD70 gained a lot of attraction due to its key role in regulating T cell activation, survival, differentiation, and maintenance, especially in the course of viral infections and cancer...
December 27, 2017: Immunology
https://www.readbyqxmd.com/read/29281733/adenoviral-vaccine-induction-of-cd8-t-cell-memory-inflation-impact-of-co-infection-and-infection-order
#20
Lian N Lee, Beatrice Bolinger, Zoltan Banki, Catherine de Lara, Andrew J Highton, Julia M Colston, Claire Hutchings, Paul Klenerman
The efficacies of many new T cell vaccines rely on generating large populations of long-lived pathogen-specific effector memory CD8 T cells. However, it is now increasingly recognized that prior infection history impacts on the host immune response. Additionally, the order in which these infections are acquired could have a major effect. Exploiting the ability to generate large sustained effector memory (i.e. inflationary) T cell populations from murine cytomegalovirus (MCMV) and human Adenovirus-subtype (AdHu5) 5-beta-galactosidase (Ad-lacZ) vector, the impact of new infections on pre-existing memory and the capacity of the host's memory compartment to accommodate multiple inflationary populations from unrelated pathogens was investigated in a murine model...
December 27, 2017: PLoS Pathogens
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