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https://www.readbyqxmd.com/read/28533942/hla-a24-ligandome-analysis-of-colon-and-lung-cancer-cells-identifies-a-novel-cancer-testis-antigen-and-a-neoantigen-that-elicits-specific-and-strong-ctl-responses
#1
Vitaly Kochin, Takayuki Kanaseki, Serina Tokita, Sho Miyamoto, Yosuke Shionoya, Yasuhiro Kikuchi, Daichi Morooka, Yoshihiko Hirohashi, Tomohide Tsukahara, Kazue Watanabe, Shingo Toji, Yasuo Kokai, Noriyuki Sato, Toshihiko Torigoe
This study focused on HLA-A24 and comprehensively analyzed the ligandome of colon and lung cancer cells without the use of MHC-binding in silico prediction algorithms. Affinity purification using the antibody specific to HLA-A24 followed by LC-MS/MS sequencing was used to detect peptides, which harbored the known characteristics of HLA-A24 peptides in terms of length and anchor motifs. Ligandome analysis demonstrated the natural presentation of two different types of novel tumor-associated antigens. The ligandome contained a peptide derived from SUV39H2, a gene found to be expressed in a variety of cancers but not in normal tissues (except for the testis)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28515346/the-novel-complex-combination-of-alum-cpg-odn-and-hh2-as-adjuvant-in-cancer-vaccine-effectively-suppresses-tumor-growth-in-vivo
#2
Yaomei Tian, Meng Li, Chaoheng Yu, Rui Zhang, Xueyan Zhang, Rong Huang, Lian Lu, Fengjiao Yuan, Yingzi Fan, Bailing Zhou, Ke Men, Heng Xu, Li Yang
Single-component adjuvant is prone to eliciting a specific type of Th1 or Th2 response. So, the development of combinatorial adjuvants inducing a robust mixed Th1/Th2 response is a promising vaccination strategy against cancer. Here, we describe a novel combination of aluminum salts (alum), CpG oligodeoxynucleotide (CpG) and innate defense regulator peptide HH2 for improving anti-tumor immune responses. The CpG-HH2 complex significantly enhanced the production of IFN-γ, TNF-α and IL-1β, promoted the uptake of antigen and strengthened the activation of p38, Erk1/2 and NF-κB in vitro, compared to CpG or HH2 alone...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28504276/targeted-calcium-influx-boosts-cytotoxic-t-lymphocyte-function-in-the-tumour-microenvironment
#3
Kyun-Do Kim, Seyeon Bae, Tara Capece, Hristina Nedelkovska, Rafael G de Rubio, Alan V Smrcka, Chang-Duk Jun, Woojin Jung, Byeonghak Park, Tae-Il Kim, Minsoo Kim
Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4(+)CD25(+)Foxp3(+) regulatory T cell (Treg) is in part mediated by TGFβ-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca(2+) response...
May 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28499492/mechanisms-and-dynamics-of-t-cell-mediated-cytotoxicity-in-vivo
#4
REVIEW
Stephan Halle, Olga Halle, Reinhold Förster
Cytotoxic T lymphocytes (CTLs) are critical in the elimination of infected or malignant cells and are emerging as a major therapeutic target. How CTLs recognize and kill harmful cells has been characterized in vitro but little is known about these processes in the living organism. Here we review recent insights into CTL-mediated killing with an emphasis on in vivo CTL biology. Specifically, we focus on the possible rate-limiting steps determining the efficiency of CTL-mediated killing. We also highlight the need for cell-based datasets that permit the quantification of CTL dynamics, including CTL location, migration, and killing rates...
May 9, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28498618/phase-i-clinical-trial-of-cell-division-associated-1-cdca1-peptide-vaccination-for-castration-resistant-prostate-cancer
#5
Wataru Obara, Fuminori Sato, Kazuyoshi Takeda, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Hiromitsu Mimata, Tamotsu Sugai, Yusuke Nakamura, Tomoaki Fujioka
We screened cell division associated 1 (CDCA1) as an oncogene that is overexpressed on several cancers, including prostate cancer. We also identified a highly immunogenic HLA-A*2402-restricted epitope peptide corresponding to part of the CDCA1 protein. We conducted a phase I clinical trial for patients with castration resistant prostate cancer (CRPC) using a CDCA1 peptide vaccination. Twelve patients having HLA-A*2402 with CRPC after failure of docetaxel chemotherapy were enrolled. They received subcutaneous administration of the CDCA1 peptide as an emulsion with Montanide ISA51VG once a week in a dose-escalation manner (doses of 1...
May 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28498408/induction-of-il-17-production-from-human-peripheral-blood-cd4-cells-by-asbestos-exposure
#6
Megumi Maeda, Ying Chen, Suni Lee, Naoko Kumagai-Takei, Kei Yoshitome, Hidenori Matsuzaki, Shoko Yamamoto, Tamayo Hatayama, Miho Ikeda, Yasumitsu Nishimura, Takemi Otsuki
We have previously reported that chronic, recurrent and low-dose exposure to asbestos fibers causes a reduction in antitumor immunity. Investigation of natural killer (NK) cells using an in vitro cell line model and comprising in vitro activation using freshly isolated NK cells co-cultured with chrysotile fibers, as well as NK cells derived from asbestos-exposed patients with pleural plaque (PP) or malignant mesothelioma (MM), revealed decreased expression of NK cell activating receptors such as NKG2D, 2B4 and NKp46...
May 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28492521/coinjection-of-il2-dna-enhances-e7-specific-antitumor-immunity-elicited-by-intravaginal-therapeutic-hpv-dna-vaccination-with-electroporation
#7
Y Sun, S Peng, A Yang, E Farmer, T-C Wu, Chien-Fu Hung
The generation and use of therapeutic human papillomavirus (HPV) DNA vaccines represent an appealing treatment method against HPV-associated cervical cancer due to their safety and durability. Previously, we created a therapeutic HPV DNA vaccine candidate by linking the HPV16-E7 DNA sequence to calreticulin (CRT/E7), which we showed could generate significant E7-specific cytotoxic T lymphocyte (CTL)-mediated anti-tumor immune responses against HPV16 oncogenes expressing murine tumor model TC-1. Here we assess the therapeutic efficacy of intravaginal immunization with pcDNA3-CRT/E7 followed by electroporation...
May 11, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28489607/trans-scirpusin-a-showed-antitumor-effects-via-autophagy-activation-and-apoptosis-induction-of-colorectal-cancer-cells
#8
Eun-Hye Hong, Eun-Young Heo, Jae-Hyoung Song, Bo-Eun Kwon, Jae-Young Lee, Yaejeong Park, Jinwoong Kim, Sun-Young Chang, Young-Won Chin, Sang-Min Jeon, Hyun-Jeong Ko
Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabellifer L. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against the tumor-associated antigen Her2, TSA treatment did not significantly increase the level of Her2-specific CTL response compared to that with vehicle treatment. However, there was a significant increase in the level of TNF-α mRNA in tumor tissue and Her2-specific Ab (antibody) production...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28488245/chimeric-antigen-receptor-car-modified-natural-killer-cell-based-immunotherapy-and-immunological-synapse-formation-in-cancer-and-hiv
#9
REVIEW
Dongfang Liu, Shuo Tian, Kai Zhang, Wei Xiong, Ndongala Michel Lubaki, Zhiying Chen, Weidong Han
Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells contribute to the body's immune defenses. Current chimeric antigen receptor (CAR)-modified T cell immunotherapy shows strong promise for treating various cancers and infectious diseases. Although CAR-modified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line. Despite recent advances in CAR-modified T cell immunotherapy, cost and severe toxicity have hindered its widespread use...
May 9, 2017: Protein & Cell
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
#10
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/28471021/syntaxin-4-mediates-endosome-recycling-for-lytic-granule-exocytosis-in-cytotoxic-t-lymphocytes
#11
Waldo A Spessott, Maria L Sanmillan, Vineet V Kulkarni, Margaret E McCormick, Claudio G Giraudo
Adaptive and innate immunity utilize the perforin-killing pathway to eliminate virus-infected or cancer cells. Cytotoxic T-lymphocytes (CTLs) and Natural Killer cells mediate this process by releasing toxic proteins at the contact area with target cells known as immunological synapse (IS). Formation of a stable IS and exocytosis of toxic proteins requires persistent fusion of Rab11a recycling endosomes with the plasma membrane (PM) that may assure the delivery of key effector proteins. Despite the importance of the recycling endosomal compartment, the membrane fusion proteins that control this process at the IS remain elusive...
May 4, 2017: Traffic
https://www.readbyqxmd.com/read/28468866/retraction-proteasome-inhibition-blocks-nf-%C3%AE%C2%BAb-and-erk1-2-pathways-restores-antigen-expression-and-sensitizes-resistant-human-melanoma-to-tcr-engineered-ctls
#12
(no author information available yet)
No abstract text is available yet for this article.
May 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28461156/quantifying-the-role-of-immunotherapeutic-drug-t11-target-structure-in-progression-of-malignant-gliomas-mathematical-modeling-and-dynamical-perspective
#13
Subhas Khajanchi, Sandip Banerjee
The paper describes a mathematical model with synergistic interaction between the malignant glioma cells and the immune system, namely, macrophages, activated Cytotoxic T-Lymphocytes (CTLs), the immunosuppressive cytokine Transforming Growth Factor - β (TGF-β) and the immuno-stimulatory cytokine Interferon - γ (IFN-γ), using a system of coupled non-linear ordinary differential equations (ODEs). We have introduced a new immunotherapeutic drug T11 Target structure (T11TS) into the model, which boosts the macrophages and CTLs to kill the glioma cells...
April 28, 2017: Mathematical Biosciences
https://www.readbyqxmd.com/read/28460461/tumor-regression-is-mediated-via-the-induction-of-her263-71-specific-cd8-ctl-activity-in-a-4t1-2-her2-tumor-model-no-involvement-of-cd80-in-tumor-control
#14
Sayyed Nilofar Danishmalik, Si-Hyeong Lee, Jeong-Im Sin
In the CT26/HER2 and 4T1.2/HER2 tumor models, CT26/HER2 cells form tumors that continue to grow, whereas 4T1.2/HER2 cells form tumors that eventually regress. Here, we investigated the differences in the behaviors of these two cell lines. When immune cells from 4T1.2/HER2 tumor-bearing animals were stimulated with HER2 class I peptides, they displayed a 2-fold increase in IFN-γ levels, in response to the peptides, HER263-71 and HER2342-350. In contrast, extremely high levels of antigen-non-specific IFN-γ production were observed with immune cells and sera from CT26/HER2 tumor-bearing mice...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454381/optimized-construction-of-muc1-vntrn-dna-vaccine-and-its-anti-pancreatic-cancer-efficacy
#15
Yuan-Feng Gong, Quan-Bo Zhou, Ya-Di Liao, Cong Mai, Tie-Jun Chen, Yun-Qiang Tang, Ru-Fu Chen
Considering mucin 1-variable number tandem repeat (MUC1-VNTRn) as a novel target for pancreatic cancer immunotherapy, the present study aimed to screen and identify the pVAX1-MUC1-VNTRn DNA vaccine with the strongest immunogenicity. Following construction of a pVAX1-MUC1-VNTRn plasmid, immature dendritic cells (DCs) were subjected to transfection, and mature DCs were then co-cultured with autologous T-cells. The numbers of cytotoxic T lymphocytes (CTLs) secreting interferon (IFN)-γ were determined using an enzyme-linked immunospot assay, and CytoTox(®) was also used to examine the MUC1-VNTRn-specific Lethal effect of CTLs on Capan2 cells...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28441623/identification-of-a-macrobrachium-nipponense-c-type-lectin-with-a-close-evolutionary-relationship-to-vertebrate-lectins
#16
Xin Huang, Tingting Li, Min Jin, Shaowu Yin, Wen Wang, Qian Ren
C-type lectins (CTLs) are involved in the innate immune defense of vertebrates and invertebrates against invading pathogens. This study cloned and characterized a novel C-type lectin (MnCTL) of the oriental river prawn, Macrobrachium nipponense. The cloned MnCTL cDNA encompasses an open reading frame of 774 nucleotides and encodes polypeptides of 257 residues. The deduced MnCTL protein contains a single carbohydrate recognition domain (CRD) with an EPN (Glu-Pro-Asn) motif in calcium-binding site 2. Phylogenetic analysis indicated that MnCTL has a closer evolutionary relationship with vertebrate lectins than with invertebrate lectins...
April 22, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28430604/signal-transducing-adaptor-protein-2-promotes-generation-of-functional-long-term-memory-cd8-t-cells-by-preventing-terminal-effector-differentiation
#17
Daisuke Muraoka, Naohiro Seo, Tae Hayashi, Chisaki Hyuga-Amaike, Kana Okamori, Isao Tawara, Naozumi Harada, Hiroshi Shiku
Long-surviving memory CD8+ T cells generated by stimulation with appropriate tumor-associated antigens are the most aggressive and persistent tumoricidal effectors. In this event of memory CD8+ T cell development, the signal transducer and activator of transcription (STAT) proteins function as the crucial intracellular signaling molecules, but the regulatory mechanism of STATs in CD8+ T cells is not fully understood. In this study, we report for the first time, by using murine vaccination models, that signal-transducing adaptor protein-2 (STAP2) maintains the cytotoxicity of long-lived memory CD8+ T cells by controlling a STAT3/suppressor of cytokine signaling 3 (SOCS3) cascade...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430349/prognostic-significance-of-infiltrating-immune-cell-subtypes-in-invasive-ductal-carcinoma-of-the-breast
#18
Yangmei Xu, Suzhen Lan, Qiuhong Zheng
PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis. MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low)...
April 20, 2017: Tumori
https://www.readbyqxmd.com/read/28425860/a-novel-recombinant-multi-epitope-vaccine-could-induce-specific-cytotoxic-t-lymphocyte-response-in-vitro-and-in-vivo
#19
Yahong Wu, Wenjie Zhai, Meng Sun, Zhe Zou, Xiuman Zhou, Guodong Li, Zhongyi Yan, Yuanming Qi, Yanfeng Gao
Cytotoxic CD8+ T lymphocytes (CTLs) play an important role in killing tumor cells. To develop therapeutic vaccines that can induce specific immune response, we designed a novel recombinant multiepitope vaccine YL66 which consists of HLA-A2-restricted CTL epitopes from two widely expressed tumor antigen cyclooxygenase-2 and MAGE-4, linked with membrane permeable Tat-PTD and the universal T helper epitope. The DNA fragment of YL66 was cloned into pGEX-4T-2-YL66 and pcDNA3.1(+)-YL66, respectively. Then, we tested whether the expressed protein GST-YL66 and DNA vaccine pcDNA3...
April 19, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28421385/in-vitro-and-in-vivo-anti-tumor-effects-of-selected-platinum-iv-and-dinuclear-platinum-ii-complexes-against-lung-cancer-cells
#20
Milos Arsenijevic, Marija Milovanovic, Snezana Jovanovic, Natalija Arsenijevic, Bojana Simovic Markovic, Marina Gazdic, Vladislav Volarevic
In the present study, cytotoxic effects of cisplatin, the most usually used chemotherapeutic agent, were compared with new designed platinum(IV) ([PtCl4(en)] (en = ethylenediamine) and [PtCl4(dach)]) (dach = (±)-trans-1,2-diaminocyclohexane) and platinum(II) complexes ([{trans-Pt(NH3)2Cl}2(μ-pyrazine)](ClO4)2 (Pt1), [{trans-Pt(NH3)2Cl}2(μ-4,4'-bipyridyl)](ClO4)2DMF(Pt2),[{trans-Pt(NH3)2Cl}2(μ-1,2-bis(4pyridyl)ethane)](ClO4)2 (Pt3)), in vitro and in vivo against human and murine lung cancer cells, to determine anti-tumor potential of newly synthesized platinum-based drugs in the therapy of lung cancer...
April 18, 2017: Journal of Biological Inorganic Chemistry: JBIC
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