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Tumor immune recognition

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https://www.readbyqxmd.com/read/28539888/safety-and-immunogenicity-of-a-human-epidermal-growth-factor-receptor-1-her1-based-vaccine-in-prostate-castration-resistant-carcinoma-patients-a-dose-escalation-phase-i-study-trial
#1
Iraida Caballero, Lazaro E Aira, Anabel Lavastida, Xitlally Popa, Javier Rivero, Joaquín González, Mónica Mesa, Narjara González, Kelly Coba, Patricia Lorenzo-Luaces, Barbara Wilkinson, Yuliannis Santiesteban, Yanela Santiesteban, Mayelin Troche, Eduardo Suarez, Tania Crombet, Belinda Sánchez, Angel Casacó, Amparo Macías, Zaima Mazorra
Metastatic castration-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Activation of the human epidermal growth factor receptor 1 (HER1) in prostate cancer contributes to metastatic progression as well as to disease relapse. Here, we determined the toxicity and immunogenicity of a HER1-based cancer vaccine in CRPC patients included in a phase I clinical trial. CRPC patients (n = 24) were intramuscularly vaccinated with HER1 vaccine consisting of the extracellular domain of HER1 molecule (ECD) and very small size proteoliposome from Neisseria meningitidis (VSSP) and Montanide ISA-51 VG as adjuvants...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#2
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533893/expression-of-pattern-recognition-receptor-genes-and-mortality-in-patients-with-colorectal-adenocarcinoma
#3
Kathryn E Royse, Liang Chen, David H Berger, Michael M Ittmann, Hashem B El-Serag, Courtney J Balentine, David Y Graham, Peter A Richardson, Rolando E Rumbaut, Xiaoyun Shen, Donna L White, Li Jiao
Toll-like receptors (TLRs) and the receptor for advanced glycation end products (AGER) are pattern recognition receptors that regulate intestinal inflammatory homeostasis. However, their relevance in colorectal cancer (CRC) prognosis is unclear. We investigated expression of TLRs, AGER, and interacting proteins in association with CRC mortality in a retrospective cohort study of 65 males diagnosed with primary resectable CRC between 2002 and 2009. Multiplex quantitative nuclease protection assay was used to quantify the expression of 19 genes in archived tissues of tumor and paired adjacent normal mucosa...
2017: International Journal of Molecular Epidemiology and Genetics
https://www.readbyqxmd.com/read/28532825/growth-performance-reproductive-traits-and-offspring-survivability-of-genetically-modified-rams-overexpressing-toll-like-receptor-4
#4
Yu-Chang Yao, Hong-Bing Han, Xu-Ting Song, Shou-Long Deng, Yu-Feng Liu, Ming-Hai Lu, Yun-Hai Zhang, Mei-Yu Qi, Hai-Juan He, Su-Mei Wang, Guo-Shi Liu, Wu Li, Zheng-Xing Lian
Genetic modification provides a means to enhancing disease resistance in animals. Toll-like receptor 4 (TLR4), a member of the TLR family, is critical for the recognition of lipopolysaccharide (LPS)/endotoxin from Gram-negative bacteria by host immune cells, which initiates cell activation and subsequently triggers a proinflammatory response to the invading pathogens. In this study, the first generation of genetically modified (GM) sheep overexpressing TLR4 was produced by microinjection for better disease resistance...
July 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28521455/kdm3a-promotes-inhibitory-cytokines-secretion-by-participating-in-tlr4-regulation-of-foxp3-transcription-in-lung-adenocarcinoma-cells
#5
Yinan Li, Wei Yang, Bin Wu, Yaqing Liu, Dongbei Li, Yantong Guo, Haiying Fu, Yi Li
Toll-like receptor 4 (TLR4) is a pattern recognition receptors, a member of the Toll-like receptor family and it serves a role in innate and acquired immunity. It has previously been reported that TLR4 was overexpressed in a variety of tumor tissues and cells, including colorectal cancer, gastric cancer and ovarian cancer. In the tumor microenvironment, the TLR4 signaling pathway may be activated in order to upregulate forkhead box P3 (Foxp3) expression in regulatory T cells (Tregs), and thus enhance the immunosuppressive function of Tregs...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28514851/blood-brain-barrier-penetrating-biologic-tnf-%C3%AE-inhibitor-for-alzheimer-s-disease
#6
Rudy Chang, Jillian Knox, Jae Chang, Aram Derbedrossian, Vitaly Vasilevko, David Cribbs, Ruben J Boado, William M Pardridge, Rachita Sumbria
OBJECTIVE: Tumor necrosis factor alpha (TNF-α) driven processes are involved at multiple stages of Alzheimer's disease (AD) pathophysiology and disease progression. Biologic TNF-α inhibitors (TNFIs) are the most potent class of TNFIs but cannot be developed for AD since these macromolecules do not cross the blood-brain barrier (BBB). A BBB-penetrating TNFI was engineered by the fusion of the extracellular domain of the type II human TNF receptor (TNFR) to a chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR), designated as the cTfRMAb-TNFR fusion protein...
May 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28511073/preparation-and-evaluation-of-l-and-d-5-18-f-fluorotryptophan-as-pet-imaging-probes-for-indoleamine-and-tryptophan-2-3-dioxygenases
#7
Tang Tang, Herman S Gill, Annie Ogasawara, Jeff N Tinianow, Alexander N Vanderbilt, Simon-Peter Williams, Georgia Hatzivassiliou, Sharla White, Wendy Sandoval, Kevin DeMent, Mengling Wong, Jan Marik
Indoleamine and tryptophan 2,3-dioxygenases (IDO1 and TDO2) are pyrrolases catalyzing the oxidative cleavage of the 2,3-double bond of L-tryptophan in kynurenine pathway. In the tumor microenvironment, their increased activity prevents normal immune function, i.e. tumor cell recognition and elimination by cytotoxic T-cells. Consequently, inhibition of the kynurenine pathway may enhance the activity of cancer immunotherapeutics by reversing immune dysfunction. We sought to investigate the properties of radiolabeled 5-[(18)F]fluorotryptophan with respect to its ability for measuring IDO1 and TDO2 activity by positron emission tomography (PET)...
May 5, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28507791/the-mutational-status-of-p53-can-influence-its-recognition-by-human-t-cells
#8
Katerina Shamalov, Shlomo N Levy, Miryam Horovitz-Fried, Cyrille J Cohen
p53 was reported to be an attractive immunotherapy target because it is mutated in approximately half of human cancers, resulting in its inactivation and often accumulation in tumor cells. Peptides derived from p53 are presented by class I MHC molecules and may act as tumor-associated epitopes which could be targeted by p53-specific T cells. Interestingly, it was recently shown that there is a lack of significant correlation between p53 expression levels in tumors and their recognition by p53-TCR transduced T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28494555/-liver-sinusoidal-endothelial-cells-regulate-adaptive-immune-tolerance-in-the-liver
#9
Y Q Du, C Sun, S M Huang, D L Yang, J Wu
Liver sinusoidal endothelial cells are a major group of nonparenchymal cells in the liver and are involved in immunological surveillance of the liver through the expression of various scavenger receptors and pattern recognition receptors. However, in case of several physiological states, viral infections, and tumor environment, liver sinusoidal endothelial cells maintain immune tolerance in the liver through various mechanisms and cause persistent viral infection and tumor metastasis. This article reviews the mechanisms of immune tolerance of CD4 + T cells and CD8 + T cells in the liver induced by liver sinusoidal endothelial cells...
April 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28494200/a-new-therapeutic-potential-for-cancers-one-car-with-2-different-engines
#10
Abdolkarim Sheikhi, Abdollah Jafarzadeh
Tumor cells escape from immune recognition by several mechanisms such as down-regulating of MHC class I molecules, losing of tumor antigens, etc. The purpose of cancer immunotherapy is to robust or reconstruct the capacity of the immune system to recognize and kill tumor cells by overwhelming the mechanisms by which tumors escape the immune response. One of the novel immunotherapeutic strategies were used to potentiate NK- and T cell functions is chimeric antigen receptor (CAR). CARs are composed of an antigen-binding domain of a molecule such as an antibody (that binds to a tumor associated antigens expressed on the surface of tumor cells) and an intracellular T cell activation domain...
May 11, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28490949/function-of-pd-l1-in-antitumor-immunity-of-glioma-cells
#11
Yongli Lou, Jin Shi, Dewei Guo, Ahmad Kaleem Qureshi, Laijun Song
Human glioma is a highly fatal tumor with a significant feature of immune suppression. The functions of PD-L1 refer to co-simulation and immune regulation. To investigate expression and functional activity of PD-L1 in human glioma cell in vivo and in vitro. Expressions of PD-L1mRNA and protein in the human glioma cell line were analyzed with quantitative RT-PCR and flow cytometer; and then expression of PD-L1 in tissue specimens of 10 glioma patients was treated with immunohistochemical analysis; glioma cell and allogeneic CD4(+) and CD8(+) T cells were co-cultured, and cytokine IFN-γ, IL-2 and IL-10 in cultured supernatant fluid were determined with ELISA; upon blocking the interaction between glioma cell and the immune cell with PD-L1 monoclonal antibody (5H1), surface markers on immune cells were analyzed using flow cytometer...
May 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28486273/zebularine-treatment-induces-mage-a11-expression-and-improves-ctl-cytotoxicity-using-a-novel-identified-hla-a2-restricted-mage-a11-peptide
#12
Jiandong Zhang, Meixiang Sang, Lina Gu, Fei Liu, Weijing Li, Danjing Yin, Yunyan Wu, Shina Liu, Weina Huang, Baoen Shan
Melanoma-associated antigen-A11 (MAGE-A11) is frequently expressed in breast cancer and is associated with poor prognosis. Therefore, MAGE-A11 is a potential immunotherapy target in breast cancer. MAGE-A11 expression, however, is downregulated in many patients, thus constraining the application of immunotherapy. The induction of MAGE-A11 expression is crucial for the recognition and killing of breast cancer cells by cytotoxic T lymphocytes (CTL). In this study, a series of HLA-A2-restricted candidate MAGE-A11 peptides were predicted, synthesized, and tested...
May 8, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28484456/expression-of-tlr4-in-non-small-cell-lung-cancer-is-associated-with-pd-l1-and-poor-prognosis-in-patients-receiving-pulmonectomy
#13
Kaiyuan Wang, Jian Wang, Feng Wei, Ning Zhao, Fan Yang, Xiubao Ren
Currently, the effect of inflammation on tumorigenesis and progression has been widely noted. As a member of pattern recognition receptors, toll-like receptor 4 (TLR4) plays a pivotal role in tumor immune microenvironment and has been increasingly investigated. In the present study, we evaluated TLR4 expression and its association with programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) tissues and assessed the predicting value of TLR4 on postoperative outcome. A total of 126 NSCLC patients receiving complete pulmonary resection and systematic lymph node dissection between April 2008 and August 2014 were enrolled...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28484076/sarcoma-eradication-by-doxorubicin-and-targeted-tnf-relies-upon-cd8-t-cell-recognition-of-a-retroviral-antigen
#14
Philipp Probst, Janine Kopp, Annette Oxenius, Mario P Colombo, Danilo Ritz, Tim Fugmann, Dario Neri
Antibody-cytokine complexes may offer new tools to treat cancer. Here we show how TNF-linked antibodies, which recognize tumor-selective splice isoforms of fibronectin (F8-TNF), can be exploited to eradicate sarcomas in immunocompetent mice. We treated mice bearing WEHI-164 fibrosarcoma with a combination of F8-TNF and doxorubicin, curing the majority of treated animals (29/37). Notably, cured mice were resistant to re-challenge not only by WEHI-164 cells but also heterologous C51 or CT26 colorectal tumor cells in a CD8+ T cell-dependent process...
May 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/28480325/the-sequence-of-delta24-rgd-and-tmz-administration-in-malignant-glioma-affects-the-role-of-cd8-t-cell-anti-tumor-activity
#15
Anne Kleijn, Wouter van den Bossche, Erik S Haefner, Zineb Belcaid, Chantal Burghoorn-Maas, Jenneke J Kloezeman, Suzan D Pas, Sieger Leenstra, Reno Debets, Jeroen de Vrij, Clemens M F Dirven, Martine L M Lamfers
The conditionally replicating oncolytic adenovirus Delta24-RGD (Ad) is currently under investigation in clinical trials for glioblastoma, including in combination with temozolomide (TMZ), the standard chemotherapy for this tumor. Previously, we showed that the efficacy of Delta24-RGD in a murine model is primarily dependent on the virus-induced anti-tumor immune response. As observed with most chemotherapies, TMZ has pronounced immune-modulating effects. Here, we studied the combined effects of these treatments in a murine glioma model...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28480306/dendritic-cell-therapies-for-hematologic-malignancies
#16
REVIEW
Matthew Weinstock, Jacalyn Rosenblatt, David Avigan
Dendritic cells (DCs) are potent antigen-presenting cells that constitute a major component of the immune system's role in the recognition, elimination, and tolerance of cancer. The unique immunologic capabilities of DCs have recently been harnessed for therapeutic use with the creation of DC-based anti-tumor vaccines, several of which have moved into testing in clinical trials for hematologic malignancies. This review summarizes how treatment strategies using DC-based anti-tumor vaccines are advancing immunotherapeutic options for these diseases...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28474278/cancer-immunotherapy-with-cytokine-induced-killer-cells
#17
Juan J Mata-Molanes, Manuel Sureda González, Belén Valenzuela Jiménez, Elena Mª Martínez Navarro, Antonio Brugarolas Masllorens
Cytokine-induced killer (CIK) cells form under certain stimulation conditions in cultures of peripheral blood mononuclear cells (PBMCs). They are a heterogeneous immune cell population and contain a high percentage of cells with a mixed T-NK phenotype (CD3+CD56+). The ready availability of a lymphocyte source, together with the high proliferative rate and potent anti-tumor activity of CIK cells, has allowed their use as immunotherapy in a wide variety of neoplasms. Cytotoxicity mediated by CD3+CD56+ T cells depends on the major histocompatibility antigen (MHC)-independent recognition of tumor cells and the activation of signaling pathways through the natural killer group 2 member D (NKG2D) cell-surface receptor...
May 4, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28472619/toll-like-receptor-4-and-hepatocellular-carcinoma-a-systematic-review
#18
REVIEW
Zahra Sepehri, Zohre Kiani, Farhad Kohan, Seyed Moayed Alavian, Saeid Ghavami
INTRODUCTION: Toll like receptor 4 (TLR4) is an extracellular pathogen recognition receptor (PRR) which recognizes a wide range of pathogens and damage associated molecular patterns (PAMPs and DAMPs). It can activate intracellular signaling and consequently transcription factors which participate in transcription from either immune related or malignancy genes. Thus, it has been hypothesized that TLR4 may be a cause of hepatocellular carcinoma (HCC). This article has reviewed the roles of TLR4 in the pathogenesis of HCC...
May 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28459041/advancing-cancer-therapy-with-present-and-emerging-immuno-oncology-approaches
#19
REVIEW
Jeff Kamta, Maher Chaar, Anusha Ande, Deborah A Altomare, Sihem Ait-Oudhia
Immuno-oncology (I-O) is a young and growing field on the frontier of cancer therapy. Contrary to cancer therapies that directly target malignant cells, I-O therapies stimulate the body's immune system to target and attack the tumor, which is otherwise invisible to, or inhibiting the immune response. To this end, several methods have been developed: First, passive therapies that enable T-cells to fight the tumor without direct manipulation, typically through binding and modifying the intracellular signaling of surface receptors...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28454292/dna-vaccine-encoding-human-papillomavirus-antigens-flanked-by-a-signal-peptide-and-a-kdel-sequence-induces-a-potent-therapeutic-antitumor-effect
#20
Jose J Perez-Trujillo, Rodolfo Garza-Morales, Jose A Barron-Cantu, Gabriel Figueroa-Parra, Aracely Garcia-Garcia, Humberto Rodriguez-Rocha, Jaime Garcia-Juarez, Gerardo E Muñoz-Maldonado, Odila Saucedo-Cardenas, Roberto Montes-De-Oca-Luna, Maria De Jesus Loera-Arias
Cellular immune responses play a critical role in the eradication of intracellular infections and malignant cells through the recognition and subsequent removal of the infection or malignant cells. Effective antigen presentation is crucial for stimulating the immune system against malignant cells. Calreticulin (CRT) has been used to improve antigen presentation. However, CRT overexpression has been previously associated with the development of pancreatic and breast cancer. The import and retention signals of CRT in the endoplasmic reticulum (ER) can be used to overcome CRT overexpression...
March 2017: Oncology Letters
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