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Memory t cell cancer

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https://www.readbyqxmd.com/read/29791768/vaccine-immunotherapy-with-arnax-induces-tumor-specific-memory-t-cells-and-durable-anti-tumor-immunity-in-mouse-models
#1
Yohei Takeda, Sumito Yoshida, Ken Takashima, Noriko Ishii-Mugikura, Hiroaki Shime, Tsukasa Seya, Misako Matsumoto
Immunological checkpoint blockade therapies benefit a limited population of cancer patients. We have previously shown that vaccine immunotherapy with TLR3-adjuvant and tumor antigen overcomes anti-programmed death ligand-1 (PD-L1) resistance in mouse tumor models. In this study, four different OVA-expressing tumor cell lines were implanted into syngeneic mice and subjected to antitumor immunotherapy using ARNAX and whole OVA protein. ARNAX is a Toll-like receptor 3-specific agonist that does not activate the MAVS pathway, and thus does not induce systemic inflammation...
May 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29790621/generation-and-application-of-human-induced-stem-cell-memory-t-it-scm-cells-for-adoptive-immunotherapy
#2
Taisuke Kondo, Yuuki Imura, Shunsuke Chikuma, Sana Hibino, Setsuko Omata-Mise, Makoto Ando, Takashi Akanuma, Mana Iizuka, Ryota Sakai, Rimpei Morita, Akihiko Yoshimura
Adoptive T cell therapy is an effective strategy for cancer immunotherapy. However, infused T cells frequently become functionally exhausted, and consequently offer a poor prognosis after transplantation into patients. Adoptive transfer of tumor antigen-specific stem cell memory T (TSCM ) cells is expected to overcome this shortcoming since TSCM cells are close to naïve T cells, but are also highly proliferative, long-lived, and produce a large number of effector T cells in response to antigen stimulation...
May 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29784854/molecular-subtype-specific-immunocompetent-models-of-high-grade-urothelial-carcinoma-reveal-differential-neoantigen-expression-and-response-to-immunotherapy
#3
Ryoichi Saito, Christof C Smith, Takanobu Utsumi, Lisa M Bixby, Jordan Kardos, Sara E Wobker, Kyle G Stewart, Shengjie Chai, Ujjawal Manocha, Kevin Matthew Byrd, Jeffrey S Damrauer, Scott E Williams, Benjamin G Vincent, William Y Kim
High-grade urothelial cancer contains intrinsic molecular subtypes that exhibit differences in underlying tumor biology and can be divided into luminal-like and basal-like subtypes. We describe here the first subtype-specific murine models of bladder cancer and show that Upk3a-CreERT2; Trp53L/L; PtenL/L; Rosa26LSL-Luc (UPPL: luminal-like) and BBN (basal-like) tumors are more faithful to human bladder cancer than the widely-used MB49 cells. Following engraftment into immunocompetent C57BL/6 mice, BBN tumors were more responsive to PD-1 inhibition than UPPL tumors...
May 21, 2018: Cancer Research
https://www.readbyqxmd.com/read/29777219/tissue-resident-memory-t-cells-at-the-center-of-immunity-to-solid-tumors
#4
REVIEW
Derk Amsen, Klaas P J M van Gisbergen, Pleun Hombrink, Rene A W van Lier
Immune responses in tissues are constrained by the physiological properties of the tissue involved. Tissue-resident memory T cells (TRM cells) are a recently discovered lineage of T cells specialized for life and function within tissues. Emerging evidence has shown that TRM cells have a special role in the control of solid tumors. A high frequency of TRM cells in tumors correlates with favorable disease progression in patients with cancer, and studies of mice have shown that TRM cells are necessary for optimal immunological control of solid tumors...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29770915/cytolytic-activity-score-to-assess-anticancer-immunity-in-colorectal-cancer
#5
Sumana Narayanan, Tsutomu Kawaguchi, Li Yan, Xuan Peng, Qianya Qi, Kazuaki Takabe
BACKGROUND: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. METHODS: Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29758330/human-liver-infiltrating-%C3%AE-%C3%AE-t-cells-are-composed-of-clonally-expanded-circulating-and-tissue-resident-populations
#6
Stuart Hunter, Carrie Willcox, Martin Davey, Sofya Kasatskaya, Hannah Jeffery, Dmitriy Chudakov, Ye Oo, Benjamin Willcox
BACKGROUND & AIM: γδ T-cells comprise a substantial proportion of tissue-associated lymphocytes. However, our current understanding of human γδ T-cells is primarily based on peripheral blood subsets, while the immunobiology of tissue-associated subsets remains largely unclear. METHODS: To address this, we characterised the TCR diversity, immunophenotype and function of human liver infiltrating γδ T-cells, focussing on the predominant tissue-associated Vδ2neg γδ subset, which is implicated in liver immunopathology...
May 11, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29755647/autologous-tumor-cells-bacillus-calmette-gu%C3%A3-rin-formalin-based-novel-breast-cancer-vaccine-induces-an-immune-antitumor-response
#7
María José Godoy-Calderón, Víctor Salazar, Eglys González-Marcano, Ana Federica Convit
Autologous cancer cell vaccines represent a multivalent patient-specific treatment. Studies have demonstrated that these immunotherapies should be combined with immunomodulators to improve results. We tested in breast cancer the antitumor effects of a 200 µg autologous tumor cells homogenate combined with 0.0625 mg of bacillus Calmette-Guérin (BCG), and 0.02% formalin. We used a 4T1 murine model of BALB/c receiving four weekly injections of either this vaccine or control treatments. The control treatments were either Phosphate Buffer Saline, BCG treated with formalin, or the tumor cells homogenate plus BCG alone...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29754771/epstein-barr-virus-specific-cytokine-induced-killer-cells-for-treatment-of-epstein-barr-virus-related-malignant-lymphoma
#8
Lisa-Marie Pfeffermann, Verena Pfirrmann, Sabine Huenecke, Melanie Bremm, Halvard Bonig, Hans-Michael Kvasnicka, Thomas Klingebiel, Peter Bader, Eva Rettinger
BACKGROUND: Prolonged immunosuppression or delayed T-cell recovery may favor Epstein-Barr virus (EBV) infection or reactivation after allogeneic hematopoietic stem cell transplantation (HSCT), which can lead to post-transplant lymphoproliferative disease (PTLD) and high-grade malignant B-cell lymphoma. Cytokine-induced killer (CIK) cells with dual specific anti-tumor and virus-specific cellular immunity may be applied in this context. METHODS: CIK cells with EBV-specificity were generated from peripheral blood mononuclear cells (PBMCs), expanded in the presence of interferon-γ, anti-CD3, interleukin (IL)-2 and IL-15 and were pulsed twice with EBV consensus peptide pool...
May 10, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29752021/hyperthermic-treatment-at-56-%C3%A2-c-induces-tumour-specific-immune-protection-in-a-mouse-model-of-prostate-cancer-in-both-prophylactic-and-therapeutic-immunization-regimens
#9
Francesco De Sanctis, Sara Sandri, Matteo Martini, Marta Mazzocco, Alessandra Fiore, Rosalinda Trovato, Stefano Garetto, Davide Brusa, Stefano Ugel, Silvia Sartoris
Most active cancer immunotherapies able to induce a long-lasting protection against tumours are based on the activation of tumour-specific cytotoxic T lymphocytes (CTLs). Cell death by hyperthermia induces apoptosis followed by secondary necrosis, with the production of factors named "danger associated molecular pattern" (DAMP) molecules (DAMPs), that activate dendritic cells (DCs) to perform antigen uptake, processing and presentation, followed by CTLs cross priming. In many published studies, hyperthermia treatment of tumour cells is performed at 42-45 °C; these temperatures mainly promote cell surface expression of DAMPs...
May 8, 2018: Vaccine
https://www.readbyqxmd.com/read/29747685/car-t-cell-therapy-for-breast-cancer-harnessing-the-tumor-milieu-to-drive-t-cell-activation
#10
Pradip Bajgain, Supannikar Tawinwung, Lindsey D'Elia, Sujita Sukumaran, Norihiro Watanabe, Valentina Hoyos, Premal Lulla, Malcolm K Brenner, Ann M Leen, Juan F Vera
BACKGROUND: The adoptive transfer of T cells redirected to tumor via chimeric antigen receptors (CARs) has produced clinical benefits for the treatment of hematologic diseases. To extend this approach to breast cancer, we generated CAR T cells directed against mucin1 (MUC1), an aberrantly glycosylated neoantigen that is overexpressed by malignant cells and whose expression has been correlated with poor prognosis. Furthermore, to protect our tumor-targeted cells from the elevated levels of immune-inhibitory cytokines present in the tumor milieu, we co-expressed an inverted cytokine receptor linking the IL4 receptor exodomain with the IL7 receptor endodomain (4/7ICR) in order to transform the suppressive IL4 signal into one that would enhance the anti-tumor effects of our CAR T cells at the tumor site...
May 10, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29742730/il-35-producing-b-cells-in-gastric-cancer-patients
#11
Ke Wang, Jianming Liu, Jiansheng Li
A significant characteristic of advanced gastric cancer (GC) is immune suppression, which can promote the progression of GC. Interleukin 35 (IL-35) is an immune-suppressing cytokine, and it is generally recognized that this cytokine is secreted by regulatory T (Treg) cells. Recently, studies have found that IL-35 can also be produced by B cells in mice. However, scientific studies reporting that IL-35 is secreted by B cells in humans, specifically in cancer patients, are very rare.Blood samples were collected from 30 healthy controls (HCs) and 50 untreated GC patients, and IL-35-producing B cells in the peripheral blood were investigated...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29738228/enhanced-tumor-retention-effect-by-click-chemistry-for-improved-cancer-immunochemotherapy
#12
Ling Mei, Yayuan Liu, Jingdong Rao, Xian Tang, Man Li, Zhirong Zhang, Qin He
Due to the limited drug concentration in tumor tissues and inappropriate treatment strategies, tumor recurrence and metastasis are critical challenges for effectively treating malignancies. A key challenge for effective delivery of nanoparticles is to reduce reticuloendothelial system uptake and to maximize the enhanced permeability and retention effect. Herein, we demonstrated that Cu(I)-catalyzed click chemistry triggered the aggregation of azide/alkyne-modified micelles, enhancing micelles accumulation in tumor tissues...
May 8, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29721531/extra-large-pore-mesoporous-silica-nanoparticles-enabling-co-delivery-of-high-amounts-of-protein-antigen-and-toll-like-receptor-9-agonist-for-enhanced-cancer-vaccine-efficacy
#13
Bong Geun Cha, Ji Hoon Jeong, Jaeyun Kim
Cancer vaccine aims to invoke antitumor adaptive immune responses to detect and eliminate tumors. However, the current dendritic cells (DCs)-based cancer vaccines have several limitations that are mostly derived from the ex vivo culture of patient DCs. To circumvent the limitations, direct activation and maturation of host DCs using antigen-carrying materials, without the need for isolation of DCs from patients, are required. In this study, we demonstrate the synthesis of extra-large pore mesoporous silica nanoparticles (XL-MSNs) and their use as a prophylactic cancer vaccine through the delivery of cancer antigen and danger signal to host DCs in the draining lymph nodes...
April 25, 2018: ACS Central Science
https://www.readbyqxmd.com/read/29721389/bacterial-ghosts-as-adjuvant-to-oxaliplatin-chemotherapy-in-colorectal-carcinomatosis
#14
Diana Groza, Sebastian Gehrig, Pavol Kudela, Martin Holcmann, Christine Pirker, Carina Dinhof, Hemma H Schueffl, Marek Sramko, Julia Hoebart, Fatih Alioglu, Michael Grusch, Manfred Ogris, Werner Lubitz, Bernhard K Keppler, Irena Pashkunova-Martic, Christian R Kowol, Maria Sibilia, Walter Berger, Petra Heffeter
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer mortality worldwide. At late stage of the disease CRC often shows (multiple) metastatic lesions in the peritoneal cavity which cannot be efficiently targeted by systemic chemotherapy. This is one major factor contributing to poor prognosis. Oxaliplatin is one of the most commonly used systemic treatment options for advanced CRC. However, drug resistance - often due to insufficient drug delivery - is still hampering successful treatment...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721385/prognosis-of-ovarian-cancer-is-associated-with-effector-memory-cd8-t-cell-accumulation-in-ascites-cxcl9-levels-and-activation-triggered-signal-transduction-in-t-cells
#15
Sonja Lieber, Silke Reinartz, Hartmann Raifer, Florian Finkernagel, Tobias Dreyer, Holger Bronger, Julia M Jansen, Uwe Wagner, Thomas Worzfeld, Rolf Müller, Magdalena Huber
The accumulation of intratumoral CD8+ T cells is associated with the survival of high grade serous ovarian carcinoma patients, but it is unclear which CD8+ T cell subsets contribute to this effect and how they are affected by the peritoneal tumor microenvironment. Here, we provide evidence for a functional link between long relapse-free survival, accumulation of CD8+ effector memory T (TEM ) cells in peritoneal effusion (ascites), and the level of the CD8+ TEM attracting chemokine CXCL9, produced by macrophages as a major source...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29713085/determinants-of-response-and-resistance-to-cd19-chimeric-antigen-receptor-car-t-cell-therapy-of-chronic-lymphocytic-leukemia
#16
Joseph A Fraietta, Simon F Lacey, Elena J Orlando, Iulian Pruteanu-Malinici, Mercy Gohil, Stefan Lundh, Alina C Boesteanu, Yan Wang, Roddy S O'Connor, Wei-Ting Hwang, Edward Pequignot, David E Ambrose, Changfeng Zhang, Nicholas Wilcox, Felipe Bedoya, Corin Dorfmeier, Fang Chen, Lifeng Tian, Harit Parakandi, Minnal Gupta, Regina M Young, F Brad Johnson, Irina Kulikovskaya, Li Liu, Jun Xu, Sadik H Kassim, Megan M Davis, Bruce L Levine, Noelle V Frey, Donald L Siegel, Alexander C Huang, E John Wherry, Hans Bitter, Jennifer L Brogdon, David L Porter, Carl H June, J Joseph Melenhorst
Tolerance to self-antigens prevents the elimination of cancer by the immune system1,2 . We used synthetic chimeric antigen receptors (CARs) to overcome immunological tolerance and mediate tumor rejection in patients with chronic lymphocytic leukemia (CLL). Remission was induced in a subset of subjects, but most did not respond. Comprehensive assessment of patient-derived CAR T cells to identify mechanisms of therapeutic success and failure has not been explored. We performed genomic, phenotypic and functional evaluations to identify determinants of response...
April 30, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29707158/differential-role-of-cxcr3-in-inflammation-and-colorectal-cancer
#17
REVIEW
Jessicca D Abron, Narendra P Singh, Angela E Murphy, Manoj K Mishra, Robert L Price, Mitzi Nagarkatti, Prakash S Nagarkatti, Udai P Singh
Chemokines (CXCR3) and their ligands (CXCL9, CXCL10, and CXCL11) exert exquisite control over T-cell trafficking and are critical for activation, differentiation and effector T cell function. CXCR3 is important for CD4 Th1 cells, CD8 effectors, memory cells, and for the function of natural killer and natural killer T cells. The presence of high cytotoxic CXCR3 ligand expression on CD8 T cells in colorectal cancerous tissue has been well documented in the past. CXCR3 and its ligands are differentially expressed at sites of inflammation and within the tumors...
April 3, 2018: Oncotarget
https://www.readbyqxmd.com/read/29691900/a-dual-immunotherapy-nanoparticle-improves-t-cell-activation-and-cancer-immunotherapy
#18
Yu Mi, Christof C Smith, Feifei Yang, Yanfei Qi, Kyle C Roche, Jonathan S Serody, Benjamin G Vincent, Andrew Z Wang
Combination immunotherapy has recently emerged as a powerful cancer treatment strategy. A promising treatment approach utilizes coadministration of antagonistic antibodies to block checkpoint inhibitor receptors, such as antiprogrammed cell death-1 (aPD1), alongside agonistic antibodies to activate costimulatory receptors, such as antitumor necrosis factor receptor superfamily member 4 (aOX40). Optimal T-cell activation is achieved when both immunomodulatory agents simultaneously engage T-cells and promote synergistic proactivation signaling...
April 25, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29691251/nfatc1-promotes-anti-tumoral-effector-functions-and-memory-cd8-t-cell-differentiation-during-non-small-cell-lung-cancer-development
#19
Lisanne Heim, Juliane Friedrich, Marina Engelhardt, Denis I Trufa, Carol I Geppert, Ralf Joachim Rieker, Horia Sirbu, Susetta Finotto
Nuclear factor of activated T cells 1 (NFATc1) is a transcription factor activated by T cell receptor (TCR) and Ca2+-signaling that affects T cell activation and effector function. Upon tumor antigen challenge, TCR and calcium-release-activated channels are induced, promoting NFAT dephosphorylation and translocation into the nucleus. In this study, we report a progressive decrease of NFATc1 in lung tumor tissue and in tumor-infiltrating lymphocytes (TIL) of patients suffering from advanced stage non-small cell lung cancer (NSCLC)...
April 24, 2018: Cancer Research
https://www.readbyqxmd.com/read/29684436/foxo-transcription-factors-in-t-cell-biology-and-tumor-immunity
#20
REVIEW
Chong T Luo, Ming O Li
The evolutionally conserved forkhead box O (Foxo) family of transcription factors is pivotal in the control of nutrient sensing and stress responses. Recent studies have revealed that the Foxo proteins have been rewired to regulate highly specialized T cell activities. Here, we review the latest advances in the understanding of how Foxo transcription factors control T cell biology, including T cell trafficking, naive T cell homeostasis, effector and memory responses, as well as the differentiation and function of regulatory T cells...
April 20, 2018: Seminars in Cancer Biology
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