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Memory t cell cancer

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https://www.readbyqxmd.com/read/28642819/adoptive-cell-therapy-using-pd-1-myeloma-reactive-t-cells-eliminates-established-myeloma-in-mice
#1
Weiqing Jing, Jill A Gershan, Grace C Blitzer, Katie Palen, James Weber, Laura McOlash, Matthew Riese, Bryon D Johnson
BACKGROUND: Adoptive cellular therapy (ACT) with cancer antigen-reactive T cells following lymphodepletive pre-conditioning has emerged as a potentially curative therapy for patients with advanced cancers. However, identification and enrichment of appropriate T cell subsets for cancer eradication remains a major challenge for hematologic cancers. METHODS: PD-1(+) and PD-1(-) T cell subsets from myeloma-bearing mice were sorted and analyzed for myeloma reactivity in vitro...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28640942/polyfunctional-response-by-immtac-imcgp100-redirected-cd8-and-cd4-t-cells
#2
Caroline Boudousquie, Giovanna Bossi, Jacob M Hurst, Karolina A Rygiel, Bent K Jakobsen, Namir J Hassan
The success of immune system based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilising monoclonal TCRs against cancer (ImmTAC(™) molecules, fusion proteins consisting of a soluble, affinity enhanced TCR and an anti-CD3 scFv Ab) were previously shown to redirect CD8(+) and CD4(+) T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognising a peptide derived from the melanoma-specific protein, gp100, presented by HLA-A*0201) efficiently redirects and activates effector and memory cells from both CD8(+) and CD4(+) repertoires...
June 22, 2017: Immunology
https://www.readbyqxmd.com/read/28637663/ny-eso-1-tcr-single-edited-central-memory-and-memory-stem-t-cells-to-treat-multiple-myeloma-without-inducing-gvhd
#3
Sara Mastaglio, Pietro Genovese, Zulma Magnani, Eliana Ruggiero, Elisa Landoni, Barbara Camisa, Giulia Schiroli, Elena Provasi, Angelo Lombardo, Andreas Reik, Nicoletta Cieri, Martina Rocchi, Giacomo Oliveira, Giulia Escobar, Monica Casucci, Bernhard Gentner, Antonello Spinelli, Anna Mondino, Attilio Bondanza, Luca Vago, Maurilio Ponzoni, Fabio Ciceri, Michael C Holmes, Luigi Naldini, Chiara Bonini
Transfer of T cell receptors (TCR) specific for tumor-associated antigens is a promising approach for cancer immunotherapy. We developed the TCR gene editing technology, that is based on the knockout of the endogenous TCR α and β genes, followed by the introduction of tumor-specific TCR genes, and that proved safer and more effective than conventional TCR gene transfer. While successful, complete editing requires extensive cell manipulation and four transduction procedures. Here we propose a novel and clinically feasible 'single TCR editing' (SE) approach, based on the disruption of the endogenous TCR α chain only, followed by the transfer of genes encoding for a tumor specific TCR...
June 21, 2017: Blood
https://www.readbyqxmd.com/read/28629381/the-era-of-bioengineering-how-will-this-affect-the-next-generation-of-cancer-immunotherapy
#4
REVIEW
Michele Graciotti, Cristiana Berti, Harm-Anton Klok, Lana Kandalaft
BACKGROUND: Immunotherapy consists of activating the patient's immune system to fight cancer and has the great potential of preventing future relapses thanks to immunological memory. A great variety of strategies have emerged to harness the immune system against tumors, from the administration of immunomodulatory agents that activate immune cells, to therapeutic vaccines or infusion of previously activated cancer-specific T cells. However, despite great recent progress many difficulties still remain, which prevent the widespread use of immunotherapy...
June 19, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28628092/tissue-resident-memory-features-are-linked-to-the-magnitude-of-cytotoxic-t-cell-responses-in-human-lung-cancer
#5
Anusha-Preethi Ganesan, James Clarke, Oliver Wood, Eva M Garrido-Martin, Serena J Chee, Toby Mellows, Daniela Samaniego-Castruita, Divya Singh, Grégory Seumois, Aiman Alzetani, Edwin Woo, Peter S Friedmann, Emma V King, Gareth J Thomas, Tilman Sanchez-Elsner, Pandurangan Vijayanand, Christian H Ottensmeier
Therapies that boost the anti-tumor responses of cytotoxic T lymphocytes (CTLs) have shown promise; however, clinical responses to the immunotherapeutic agents currently available vary considerably, and the molecular basis of this is unclear. We performed transcriptomic profiling of tumor-infiltrating CTLs from treatment-naive patients with lung cancer to define the molecular features associated with the robustness of anti-tumor immune responses. We observed considerable heterogeneity in the expression of molecules associated with activation of the T cell antigen receptor (TCR) and of immunological-checkpoint molecules such as 4-1BB, PD-1 and TIM-3...
June 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28614804/in-vivo-kinetics-and-nonradioactive-imaging-of-rapidly-proliferating-cells-in-graft-versus-host-disease
#6
Nataliya P Buxbaum, Donald E Farthing, Natella Maglakelidze, Martin Lizak, Hellmut Merkle, Andrea C Carpenter, Brittany U Oliver, Veena Kapoor, Ehydel Castro, Gregory A Swan, Liliane M Dos Santos, Nicolas J Bouladoux, Catherine V Bare, Francis A Flomerfelt, Michael A Eckhaus, William G Telford, Yasmine Belkaid, Remy J Bosselut, Ronald E Gress
Hematopoietic stem cell transplantation (HSCT) offers a cure for cancers that are refractory to chemotherapy and radiation. Most HSCT recipients develop chronic graft-versus-host disease (cGVHD), a systemic alloimmune attack on host organs. Diagnosis is based on clinical signs and symptoms, as biopsies are risky. T cells are central to the biology of cGVHD. We found that a low Treg/CD4+ T effector memory (Tem) ratio in circulation, lymphoid, and target organs identified early and established mouse cGVHD. Using deuterated water labeling to measure multicompartment in vivo kinetics of these subsets, we show robust Tem and Treg proliferation in lymphoid and target organs, while Tregs undergo apoptosis in target organs...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28606939/transcriptional-and-epigenetic-regulation-of-t-cell-hyporesponsiveness
#7
REVIEW
Renata M Pereira, Patrick G Hogan, Anjana Rao, Gustavo J Martinez
Naive CD8(+) T cells differentiate into effector and memory cytolytic T cells (CTLs) during an acute infection. In contrast, in scenarios of persistent antigen stimulation, such as chronic infections and cancer, antigen-specific CTLs show a gradual decrease in effector function, a phenomenon that has been termed CD8(+) T cell "exhaustion" or "dysfunction." Another hyporesponsive state, termed anergy, is observed when T cells are activated in the absence of positive costimulatory signals. Among the many negative regulators induced in hyporesponsive T cells are inhibitory cell-surface receptors, such as PD-1, LAG-3, CTLA-4, and TIM-3; "checkpoint blockade" therapies that involve treatment of patients with cancer with blocking antibodies to those receptors show considerable promise in the clinic because the blocking antibodies can mitigate hyporesponsiveness and promote tumor rejection...
June 12, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28600287/enrichment-of-human-ccr6-regulatory-t-cells-with-superior-suppressive-activity-in-oral-cancer
#8
Jang-Jaer Lee, Kung-Chi Kao, Yen-Ling Chiu, Chiau-Jing Jung, Chung-Ji Liu, Shih-Jung Cheng, Yen-Liang Chang, Jenq-Yuh Ko, Jean-San Chia
Human oral squamous cell carcinoma (OSCC) constitutes an inflammatory microenvironment enriched with chemokines such as CCL20, which promote cancer cell invasion and tumor progression. We found that in OSCC there is a correlation between the expression of CCL20 and FOXP3 mRNA. Therefore, we hypothesized that OSCC may favor the recruitment and retention of regulatory T (Treg) cells that express the CCL20 receptor, CCR6. Interestingly, most (∼60%) peripheral blood Treg cells express CCR6, and CCR6(+) Treg cells exhibit an activated effector/memory phenotype...
June 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28583547/major-histocompatibilty-complex-restricted-adaptive-immune-responses-to-ct26-colon-cancer-cell-line-in-mixed-allogeneic-chimera
#9
K W Lee, B Choi, Y M Kim, C W Cho, H Park, J I Moon, G-S Choi, J B Park, S J Kim
BACKGROUND: Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance as an anti-cancer therapy is yet unknown. We introduced a mixed allogenic chimera setting with the use of a murine colon cancer cell line, CT26, by performing double bone marrow transplantation. METHODS: We analyzed donor- and recipient-restricted anti-cancer T-cell responses, and phenotypes of subpopulations of T cells...
June 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28574843/characterization-of-tumor-associated-t-lymphocyte-subsets-and-immune-checkpoint-molecules-in-head-and-neck-squamous-cell-carcinoma
#10
Axel Lechner, Hans Schlößer, Sacha I Rothschild, Martin Thelen, Sabrina Reuter, Peter Zentis, Alexander Shimabukuro-Vornhagen, Sebastian Theurich, Kerstin Wennhold, Maria Garcia-Marquez, Lars Tharun, Alexander Quaas, Astrid Schauss, Jörg Isensee, Tim Hucho, Christian Huebbers, Michael von Bergwelt-Baildon, Dirk Beutner
The composition of tumor-infiltrating lymphocytes (TIL) reflects biology and immunogenicity of cancer. Here, we characterize T-cell subsets and expression of immune checkpoint molecules in head and neck squamous cell carcinoma (HNSCC). We analyzed TIL subsets in primary tumors (n = 34), blood (peripheral blood mononuclear cells (PBMC); n = 34) and non-cancerous mucosa (n = 7) of 34 treatment-naïve HNSCC patients and PBMC of 15 healthy controls. Flow cytometry analyses revealed a highly variable T-cell infiltration mainly of an effector memory phenotype (CD45RA-/CCR7-)...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28570278/cxcl13-producing-tfh-cells-link-immune-suppression-and-adaptive-memory-in-human-breast-cancer
#11
Chunyan Gu-Trantien, Edoardo Migliori, Laurence Buisseret, Alexandre de Wind, Sylvain Brohée, Soizic Garaud, Grégory Noël, Vu Luan Dang Chi, Jean-Nicolas Lodewyckx, Céline Naveaux, Hugues Duvillier, Stanislas Goriely, Denis Larsimont, Karen Willard-Gallo
T follicular helper cells (TFH cells) are important regulators of antigen-specific B cell responses. The B cell chemoattractant CXCL13 has recently been linked with TFH cell infiltration and improved survival in human cancer. Although human TFH cells can produce CXCL13, their immune functions are currently unknown. This study presents data from human breast cancer, advocating a role for tumor-infiltrating CXCL13-producing (CXCR5-) TFH cells, here named TFHX13 cells, in promoting local memory B cell differentiation...
June 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/28566332/oncolytic-adenovirus-and-tumor-targeting-immune-modulatory-therapy-improve-autologous-cancer-vaccination
#12
Hong Jiang, Yisel Rivera-Molina, Karen Clise-Dwyer, Laura Bover, Luis Vence, Ying Yuan, Frederick F Lang, Carlo Toniatti, Mohammad B Hossain, Candelaria Gomez-Manzano, Juan Fueyo
Oncolytic viruses selectively lyse tumor cells, disrupt immunosuppression within the tumor and reactivate anti-tumor immunity, but they have yet to live up to their therapeutic potential. Immune checkpoint modulation has been efficacious in a variety of cancer with an immunogenic microenvironment, but is associated with toxicity due to nonspecific T-cell activation. Therefore, combining these two strategies would likely result in both effective and specific cancer therapy. To test the hypothesis, we first constructed oncolytic adenovirus Delta-24-RGDOX expressing the immune co-stimulator OX40 ligand (OX40L)...
May 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28564620/survivin-in-autoimmune-diseases
#13
REVIEW
G Gravina, C Wasén, M J Garcia-Bonete, M Turkkila, M C Erlandsson, S Töyrä Silfverswärd, M Brisslert, R Pullerits, K M Andersson, G Katona, M I Bokarewa
Survivin is a protein functionally important for cell division, apoptosis, and possibly, for micro-RNA biogenesis. It is an established marker of malignant cell transformation. In non-malignant conditions, the unique properties of survivin make it indispensable for homeostasis of the immune system. Indeed, it is required for the innate and adaptive immune responses, controlling differentiation and maintenance of CD4(+) and CD8(+) memory T-cells, and in B cell maturation. Recently, survivin has emerged as an important player in the pathogenesis of autoimmune diseases...
May 28, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28562153/increased-frequencies-of-circulating-and-tumor-resident-v%C3%AE-1-t-cells-in-patients-with-diffuse-large-b-cell-lymphoma
#14
Emilie Reboursiere, Anne-Claire Gac, Anthony Garnier, Véronique Salaun, Oumedaly Reman, Anne-Dominique Pham, Quentin Cabrera, Kathy Khoy, Jean-Pierre Vilque, Christophe Fruchart, Sylvain Chantepie, Hyacinthe Johnson-Ansah, Margaret Macro, Stéphane Cheze, Khaled Benabed, Jean-Baptiste Mear, Xavier Troussard, Gandhi Damaj, Brigitte Le Mauff, Olivier Toutirais
Gamma-delta (γδ) T cells contribute to the innate immune response against cancer. In samples of 20 patients upon DLBCL diagnosis, we found that Vδ1(+) T cells were the major γδ T cell subset in tumors and PBMCs of patients, while Vδ2 T cells were preponderant in PBMCs of healthy subjects. Interestingly, the germinal center (GC) subtype was associated with an increase in Vδ1(+) T cells in tumors, whereas the non-GC subtype was associated with a lower frequency of γδ T cells. While circulating Vδ1(+) T cells of patients or HSs mostly exhibited a naïve phenotype, the majority of tumor Vδ1(+) T cells showed a central memory phenotype...
May 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28557197/impaired-immune-function-in-children-and-adults-with-fanconi-anemia
#15
Kasiani C Myers, Sharon Sauter, Xue Zhang, Jacob J Bleesing, Stella M Davies, Susanne I Wells, Parinda A Mehta, Ashish Kumar, Daniel Marmer, Rebecca Marsh, Darron Brown, Melinda Butsch Kovacic
BACKGROUND: Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA. PROCEDURE: We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies. Comprehensive quantitative and functional immunologic assessment of 29 FA individuals was compared to healthy age-matched controls...
May 30, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28555838/spontaneous-cd4-and-cd8-t-cell-responses-directed-against-cancer-testis-antigens-are-present-in-the-peripheral-blood-of-testicular-cancer-patients
#16
Hayden Pearce, Paul Hutton, Shalini Chaudhri, Emilio Porfiri, Prashant Patel, Richard Viney, Paul Ah Moss
Cancer/Testis Antigen (CTAg) expression is restricted to spermatogenic cells in an immune-privileged site within the testis. However, these proteins are expressed aberrantly by malignant cells and T cell responses against CTAgs develop in many cancer patients. We investigated the prevalence, magnitude and phenotype of CTAg-specific T cells in the blood of patients with testicular germ cell tumors (TGCTs). CD8(+) and CD4(+) T cell responses against MAGE-A family antigens were present in 44% (20/45) of patients' samples assayed by ex vivo IFN-γ ELISPOT...
May 28, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28550793/acute-gonadotropin-releasing-hormone-agonist-treatment-enhances-extinction-memory-in-male-rats
#17
L Y Maeng, M B Taha, K K Cover, S S Glynn, M Murillo, K Lebron-Milad, M R Milad
Leuprolide acetate (LEU), also known as Lupron, is commonly used to treat prostate cancer in men. As a gonadotropin-releasing hormone (GnRH) receptor agonist, it initially stimulates the release of gonadal hormones, testosterone (T) and estradiol. This surge eventually suppresses these hormones, preventing the further growth and spread of cancer cells. Individuals receiving this treatment often report anxiety and cognitive changes, but LEU's effects on the neural mechanisms that are involved in anxiety during the trajectory of treatment are not well known...
May 17, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28537262/induction-of-resident-memory-t-cells-enhances-the-efficacy-of-cancer-vaccine
#18
Mevyn Nizard, Hélène Roussel, Mariana O Diniz, Soumaya Karaki, Thi Tran, Thibault Voron, Estelle Dransart, Federico Sandoval, Marc Riquet, Bastien Rance, Elie Marcheteau, Elizabeth Fabre, Marion Mandavit, Magali Terme, Charlotte Blanc, Jean-Baptiste Escudie, Laure Gibault, Françoise Le Pimpec Barthes, Clemence Granier, Luis C S Ferreira, Cecile Badoual, Ludger Johannes, Eric Tartour
Tissue-resident memory T cells (Trm) represent a new subset of long-lived memory T cells that remain in tissue and do not recirculate. Although they are considered as early immune effectors in infectious diseases, their role in cancer immunosurveillance remains unknown. In a preclinical model of head and neck cancer, we show that intranasal vaccination with a mucosal vector, the B subunit of Shiga toxin, induces local Trm and inhibits tumour growth. As Trm do not recirculate, we demonstrate their crucial role in the efficacy of cancer vaccine with parabiosis experiments...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28536100/depletion-of-tumor-associated-macrophages-with-a-csf-1r-kinase-inhibitor-enhances-antitumor-immunity-and-survival-induced-by-dc-immunotherapy
#19
Floris Dammeijer, Lysanne A Lievense, Margaretha E H Kaijen-Lambers, Menno van Nimwegen, Koen Bezemer, Joost P Hegmans, Thorbald van Hall, Rudi W Hendriks, Joachim G Aerts
New immunotherapeutic strategies are needed to induce effective anti-tumor immunity in all cancer patients. Malignant mesothelioma is characterized by a poor prognosis and resistance to conventional therapies. Infiltration of tumor-associated macrophages (TAM) is prominent in mesothelioma and is linked to immune suppression, angiogenesis and tumor aggressiveness. Therefore, TAM depletion could potentially reactivate anti-tumor immunity. We show that M-CSFR-inhibition using the CSF-1R kinase inhibitor PLX3397 (pexidartinib) effectively reduced numbers of TAMs, circulating nonclassical monocytes, as well as amount of neo-angiogenesis and ascites in mesothelioma mouse models, but did not improve survival...
May 23, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28530241/notch-mediated-conversion-of-activated-t-cells-into-stem-cell-memory-like-t-cells-for-adoptive-immunotherapy
#20
Taisuke Kondo, Rimpei Morita, Yuumi Okuzono, Hiroko Nakatsukasa, Takashi Sekiya, Shunsuke Chikuma, Takashi Shichita, Mitsuhiro Kanamori, Masato Kubo, Keiko Koga, Takahiro Miyazaki, Yoshiaki Kassai, Akihiko Yoshimura
Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8(+) TSCM cells can be generated in vitro from naive CD8(+) T cells via Wnt signalling; however, methods do not yet exist for inducing TSCM cells from activated or memory T cells. Here, we show a strategy for generating TSCM-like cells in vitro (iTSCM cells) from activated CD4(+) and CD8(+) T cells in mice and humans by coculturing with stromal cells that express a Notch ligand...
May 22, 2017: Nature Communications
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