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https://www.readbyqxmd.com/read/28633645/generation-of-populations-of-antigen-specific-cytotoxic-t-cells-using-dcs-transfected-with-dna-construct-encoding-her2-neu-tumor-antigen-epitopes
#1
Maria Kuznetsova, Julia Lopatnikova, Julia Khantakova, Rinat Maksyutov, Amir Maksyutov, Sergey Sennikov
BACKGROUND: Recent fundamental and clinical studies have confirmed the effectiveness of utilizing the potential of the immune system to remove tumor cells disseminated in a patient's body. Cytotoxic T lymphocytes (CTLs) are considered the main effectors in cell-mediated antitumor immunity. Approaches based on antigen presentation to CTLs by dendritic cells (DCs) are currently being intensively studied, because DCs are more efficient in tumor antigen presentation to T cells through their initiation of strong specific antitumor immune responses than other types of antigen-presenting cells...
June 20, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#2
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28630054/slc45a2-a-melanoma-antigen-with-high-tumor-selectivity-and-reduced-potential-for-autoimmune-toxicity
#3
Jungsun Park, Amjad H Talukder, Seonah Lim, Kwanghee Kim, Ke Pan, Brenda Melendez, Sherille D Bradley, Kyle Jackson, Jahan S Khalili, Junmei Wang, Caitlin Creasy, Bih-Fang Pan, Scott E Woodman, Chantale Bernatchez, David Hawke, Patrick Hwu, Kyung-Mi Lee, Jason Roszik, Gregory Lizee, Cassian Yee
Cytotoxic T lymphocyte (CTL)-based immunotherapies have had remarkable success at generating objective clinical responses in patients with advanced metastatic melanoma.  Although the melanocyte differentiation antigens (MDAs) MART-1, PMEL, and tyrosinase were among the first melanoma tumor-associated antigens identified and targeted with immunotherapy, expression within normal melanocytes of the eye and inner ear can elicit serious autoimmune side effects, thus limiting their clinical potential as CTL targets...
June 19, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28629761/cytokines-for-the-induction-of-antitumor-effectors-the-paradigm-of-cytokine-induced-killer-cik-cells
#4
Elisa Cappuzzello, Roberta Sommaggio, Paola Zanovello, Antonio Rosato
Cytokine-Induced killer (CIK) cells are raising growing interest in cellular antitumor therapy, as they can be easily expanded with a straightforward and inexpensive protocol, and are safe requiring only GMP-grade cytokines to obtain very high amounts of cytotoxic cells. CIK cells do not need antigen-specific stimuli to be activated and proliferate, as they recognize and destroy tumor cells in an HLA-independent fashion through the engagement of NKG2D. In several preclinical studies and clinical trials, CIK cells showed a reduced alloreactivity compared to conventional T cells, even when challenged across HLA-barriers; only in a few patients, a mild GVHD occurred after treatment with allogeneic CIK cells...
June 3, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28628042/a-therapeutic-t-cell-receptor-mimic-antibody-targets-tumor-associated-prame-peptide-hla-i-antigens
#5
Aaron Y Chang, Tao Dao, Ron S Gejman, Casey A Jarvis, Andrew Scott, Leonid Dubrovsky, Melissa D Mathias, Tatyana Korontsvit, Victoriya Zakhaleva, Michael Curcio, Ronald C Hendrickson, Cheng Liu, David A Scheinberg
Preferentially expressed antigen in melanoma (PRAME) is a cancer-testis antigen that is expressed in many cancers and leukemias. In healthy tissue, PRAME expression is limited to the testes and ovaries, making it a highly attractive cancer target. PRAME is an intracellular protein that cannot currently be drugged. After proteasomal processing, the PRAME300-309 peptide ALYVDSLFFL (ALY) is presented in the context of human leukocyte antigen HLA-A*02:01 molecules for recognition by the T cell receptor (TCR) of cytotoxic T cells...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28624373/acute-tubulointerstitial-nephritis-in-an-hla-b27-positive-patient-with-axial-spondyloarthritis-being-treated-with-adalimumab
#6
David Castro Corredor, María Dolores Sánchez de la Nieta, Isabel María de Lara Simón
Antagonists of tumor necrosis factor-alpha (ATNF) are used for the treatment of multiple diseases such as psoriatic arthritis, Crohn's disease, ankylosing spondylitis and juvenile idiopathic arthritis, usually, when they are refractory to first-line treatment(1). The use of ATNF has been associated with the induction of autoimmune diseases such as systemic lupus erythematosus-like disease, vasculitis, sarcoidosis-like diseases and, recently, acute granulomatous tubulointerstitial nephritis. We report a case of acute nongranulomatous tubulointerstitial nephritis in an HLA-B27-positive patient with axial spondyloarthritis and Crohn's disease being treated with adalimumab...
June 14, 2017: Reumatología Clinica
https://www.readbyqxmd.com/read/28620375/comparative-gene-expression-analysis-of-lymphocytes-treated-with-exosomes-derived-from-ovarian-cancer-and-ovarian-cysts
#7
Yujuan Li, Yang Yang, Aiwei Xiong, Xiaoqin Wu, Jingyan Xie, Suping Han, Shuli Zhao
Cancer cells employ many strategies to evade immune defense and to facilitate tumor growth and angiogenesis. As a novel mode of intercellular communication, cancer-derived exosomes contribute to the recruitment and mediation of lymphocytes within the tumor environment. However, the mechanisms and key molecules mediating the effect of exosomes on lymphocytes are unclear. We treated healthy peripheral blood lymphocytes with exosomes from ovarian cancer and ovarian cysts and screened for differentially expressed genes using the RT(2) Profiler Cancer Inflammation and Immunity Crosstalk PCR Array...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28619968/breast-cancer-neoantigens-can-induce-cd8-t-cell-responses-and-antitumor-immunity
#8
Xiuli Zhang, Samuel Kim, Jasreet Hundal, John M Herndon, Shunqiang Li, Allegra A Petti, Savas D Soysal, Lijin Li, Michael D McLellan, Jeremy Hoog, Tina Primeau, Nancy Myers, Tammi L Vickery, Mark Sturmoski, Ian S Hagemann, Christopher A Miller, Matthew J Ellis, Elaine R Mardis, Ted Hansen, Timothy P Fleming, Peter Goedegebuure, William E Gillanders
Next-generation sequencing technologies have provided insights into the biology and mutational landscape of cancer. Here we evaluate the relevance of cancer neoantigens in human breast cancers. Using patient-derived xenografts from three patients with advanced breast cancer (xenografts were designated as WHIM30, WHIM35, and WHIM37), we sequenced exomes of tumor and patient-matched normal cells. We identified 2091 (WHIM30), 354 (WHIM35), and 235 (WHIM37) nonsynonymous somatic mutations. A computational analysis identified and prioritized HLA class I-restricted candidate neoantigens expressed in the dominant tumor clone...
June 15, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28619747/successful-immune-checkpoint-blockade-in-a-patient-with-advanced-stage-microsatellite-unstable-biliary-tract-cancer
#9
Elena Czink, Matthias Kloor, Benjamin Goeppert, Stefan Froehling, Sebastian Uhrig, Tim F Weber, Joern Meinel, Christian Sutter, Karl Heinz Weiss, Peter Schirmacher, Magnus von Knebel Doeberitz, Dirk Jaeger, Christoph Springfeld
Cancers acquire multiple somatic mutations that can lead to the generation of immunogenic mutation-induced neoantigens. These neoantigens can be recognized by the host's immune system. However, continuous stimulation of immune cells against tumor antigens can lead to immune cell exhaustion, which allows uncontrolled outgrowth of tumor cells. Recently, immune checkpoint inhibitors have emerged as a novel approach to overcome immune cell exhaustion and re-activate anti-tumor immune responses. In particular, antibodies blocking the exhaustion-mediating programmed death receptor (PD-1)/PD-L1 pathway have shown clinical efficacy...
June 15, 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28617827/nog-hil-4-tg-a-new-humanized-mouse-model-for-producing-tumor-antigen-specific-igg-antibody-by-peptide-vaccination
#10
Yoshie Kametani, Ikumi Katano, Asuka Miyamoto, Yusuke Kikuchi, Ryoji Ito, Yukari Muguruma, Banri Tsuda, Sonoko Habu, Yutaka Tokuda, Kiyoshi Ando, Mamoru Ito
Immunodeficient mice transplanted with human peripheral blood mononuclear cells (PBMCs) are promising tools to evaluate human immune responses to vaccines. However, these mice usually develop severe graft-versus-host disease (GVHD), which makes estimation of antigen-specific IgG production after antigen immunization difficult. To evaluate antigen-specific IgG responses in PBMC-transplanted immunodeficient mice, we developed a novel NOD/Shi-scid-IL2rγnull (NOG) mouse strain that systemically expresses the human IL-4 gene (NOG-hIL-4-Tg)...
2017: PloS One
https://www.readbyqxmd.com/read/28612127/expression-and-clinical-significance-of-herpes-virus-entry-mediator-hvem-in-breast-cancer
#11
Julia Y S Tsang, Kit-Wing Chan, Yun-Bi Ni, Thazin Hlaing, Jintao Hu, Siu-Ki Chan, Sai-Yin Cheung, Gary M Tse
BACKGROUND: Immune checkpoint blockades are currently actively investigated in invasive breast cancers. Given the complexity of immune regulation, multiple inhibitory molecules within the immune checkpoint framework would be involved in tumor immune escape. Evaluation of the components within the framework is a prerequisite for not only identification of additional treatment targets and optimization of immunotherapeutic strategies but also understanding the prognostic value of these molecules...
June 13, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28611304/immune-profiling-of-nf1-associated-tumors-reveals-histologic-subtype-distinctions-and-heterogeneity-implications-for-immunotherapy
#12
Kellie B Haworth, Michael A Arnold, Christopher R Pierson, Kwangmin Choi, Nicholas D Yeager, Nancy Ratner, Ryan D Roberts, Jonathan L Finlay, Timothy P Cripe
Successful treatment of neurofibromatosis type 1 (NF1)-associated tumors poses a significant clinical challenge. While the primary underlying genetic defect driving RAS signaling is well described, recent evidence suggests immune dysfunction contributes to tumor pathogenesis and malignant transformation. As immunologic characterizations, prognostic and predictive of immunotherapeutic clinical response in other cancers, are not fully described for benign and malignant NF1-related tumors, we sought to define their immunologic profiles...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28604557/antigen-presentation-by-individually-transferred-hla-class-i-genes-in-hla-a-hla-b-hla-c-null-human-cell-line-generated-using-the-multiplex-crispr-cas9-system
#13
Cheol-Hwa Hong, Hyun-Jung Sohn, Hyun-Joo Lee, Hyun-Il Cho, Tai-Gyu Kim
Human leukocyte antigens (HLAs) are essential immune molecules that affect transplantation and adoptive immunotherapy. When hematopoietic stem cells or organs are transplanted with HLA-mismatched recipients, graft-versus-host disease or graft rejection can be induced by allogeneic immune responses. The function of each HLA allele has been studied using HLA-deficient cells generated from mutant cell lines or by RNA interference, zinc finger nuclease, and the CRISPR/Cas9 system. To improve HLA gene editing, we attempted to generate an HLA class I null cell line using the multiplex CRISPR/Cas9 system by targeting exons 2 and 3 of HLA-A, HLA-B, and HLA-C genes simultaneously...
July 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28602029/the-prognostic-impact-of-programmed-cell-death-ligand-1-and-human-leukocyte-antigen-class-i-in-pancreatic-cancer
#14
Daisuke Imai, Tomoharu Yoshizumi, Shinji Okano, Hideaki Uchiyama, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Yuji Soejima, Shinichi Aishima, Yoshinao Oda, Yoshihiko Maehara
Pancreatic ductal adenocarcinoma (PDA) is associated with an immunosuppressive tumor-microenvironment (TME) that supports the growth of tumors and mediates tumors enabling evasion of the immune system. Expression of programmed cell death ligand 1 (PD-L1) and loss of human leukocyte antigen (HLA) class I on tumor cells are methods by which tumors escape immunosurveillance. We examined immune cell infiltration, the expression of PD-L1 and HLA class I by PDA cells, and the correlation between these immunological factors and clinical prognosis...
June 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28599791/characterization-of-hpv18-e6-specific-t-cell-responses-and-establishment-of-hpv18-e6-expressing-tumor-model
#15
Ying Ma, Andrew Yang, Shiwen Peng, Jin Qiu, Emily Farmer, Chien-Fu Hung, T-C Wu
Human papillomavirus (HPV) has been identified as the primary etiologic factor of cervical cancer, and subsets of anogenital and oropharyngeal cancers. HPV18 is the second most prevalent high-risk HPV type after HPV16. Furthermore, HPV18 is responsible for approximately 12% of cervical squamous cell carcinoma and 37% of cervical adenocarcinoma cases worldwide. In this study, we aimed to characterize the HPV18-E6-specific epitope and establish an HPV18 animal tumor model to evaluate the E6-specific immune response induced by our DNA vaccine...
June 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28599462/detection-of-tax-specific-ctls-in-lymph-nodes-of-adult-t-cell-leukemia-lymphoma-patients-and-its-association-with-foxp3-positivity-of-regulatory-t-cell-function
#16
Ayako Ichikawa, Hiroaki Miyoshi, Fumiko Arakawa, Junichi Kiyasu, Kensaku Sato, Daisuke Niino, Yoshizo Kimura, Maki Yoshida, Riko Kawano, Hiroko Muta, Yasuo Sugita, Koichi Ohshima
Human T-cell lymphotropic virus type (HTLV)-1 Tax is a viral protein that has been reported to be important in the proliferation of adult T-cell leukemia/lymphoma (ATLL) cells and to be a target of HTLV-1-specific cytotoxic T lymphocytes (CTLs). However, it is not clear how Tax-specific CTLs behave in lymph nodes of ATLL patients. The present study analyzed the immunostaining of Tax-specific CTLs. Furthermore, ATLL tumor cells are known to be positive for forkhead box P3 (Foxp3)and to have a regulatory T (Treg)-cell-like function...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28596474/lenalidomide-increases-human-dendritic-cell-maturation-in-multiple-myeloma-patients-targeting-monocyte-differentiation-and-modulating-mesenchymal-stromal-cell-inhibitory-properties
#17
Federica Costa, Rosanna Vescovini, Marina Bolzoni, Valentina Marchica, Paola Storti, Denise Toscani, Fabrizio Accardi, Laura Notarfranchi, Benedetta Dalla Palma, Cristina Manferdini, Sabrina Manni, Giannalisa Todaro, Gina Lisignoli, Francesco Piazza, Franco Aversa, Nicola Giuliani
The use of Lenalidomide (LEN), to reverse tumor-mediated immune suppression and amplify multiple myeloma-specific immunity is currently being explored. Particularly, LEN effects on dendritic cells (DCs) are still unclear. In this study, we investigated the potential effect of LEN on DC differentiation and activity. DCs were differentiated either from CD14+ cells obtained from patients with multiple myeloma or from a human monocytic cell line.LEN, at the concentration range reached in vivo, significantly increased the median intensity expression of HLA-DR, CD86 and CD209 by DCs derived from both bone marrow and peripheral myeloma monocytes and enhanced the production of Interleukin-8, C-C motif chemokine ligand (CCL) 2, CCL5 and tumor necrosis factor-α...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28592758/haploidentical-transplantation-using-post-transplant-high-dose-cyclophosphamide-for-adult-t-cell-lymphoma-after-mogamulizumab-treatment
#18
Manabu Kusakabe, Naoki Kurita, Hidekazu Nishikii, Rie Sato, Chikashi Yoshida, Yasuhisa Yokoyama, Mamiko Sakata-Yanagimoto, Naoshi Obara, Yuichi Hasegawa, Shigeru Chiba
A 53-year-old man diagnosed with adult T-cell lymphoma (ATL) was treated with mLSG15 chemotherapy and achieved a first complete remission. Subsequently, a liver tumor emerged that was pathologically diagnosed as ATL (first relapse). A second remission was achieved after local irradiation and four cycles of mogamulizumab treatment. The patient received peripheral blood stem cell transplantation (HSCT) from a one haplotype HLA-mismatched daughter after total body irradiation and the administration of fludarabine as a myeloablative conditioning regimen, followed by post-transplant cyclophosphamide...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28591700/restoration-of-immune-surface-molecules-in-kaposi-sarcoma-associated-herpesvirus-infected-cells-by-lenalidomide-and-pomalidomide
#19
David A Davis, Suraj Mishra, Holda A Anagho, Ashley I Aisabor, Prabha Shrestha, Victoria Wang, Yuki Takamatsu, Kenji Maeda, Hiroaki Mitsuya, Jerome B Zeldis, Robert Yarchoan
Kaposi sarcoma-associated herpesvirus (KSHV) is the cause of several tumors, including Kaposi sarcoma and primary effusion lymphoma (PEL). Most viruses have evolved means of escaping immune recognition. KSHV downregulates MHC-I expression during lytic infection, and expression of ICAM-1 and B7-2 (CD86) during latent infection, allowing evasion of T cell and natural killer immunity respectively. These effects are largely mediated by two KSHV-encoded proteins, K3 and K5. We show here that lenalidomide (Len) and pomalidomide (Pom) prevent down-regulation of MHC-I during lytic activation, and restore ICAM-1 and B7-2 surface expression in latently infected PEL cells...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591688/qa-2-expression-levels-is-related-with-tumor-infiltrating-lymphocytes-profile-during-solid-ehrlich-tumor-development
#20
Istéfani Luciene da Silva, Emerson Soares Veloso, Ivy Nayra Nascimento Gonçalves, Ariadne Duarte Braga, Miriam Teresa Paz Lopes, Geovanni Dantas Cassali, Miguel Quintanilla, Renata Toscano Simões, Enio Ferreira
The Qa-2 has been described as Human Leucocyte Antigen G (HLA-G) murine homolog. This homology is well accepted to gene and protein structure, in different pathology process and embryos implantation. However, in some neoplasm, this homology is questioned, where Qa-2 has been proposed as an immunogenic molecule, associated to tumor rejection. In this way, the aim of this study was to describe the pattern of Qa-2 expression and its relationship with the profile of tumor-infiltrating lymphocytes in solid Ehrlich tumor...
June 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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