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https://www.readbyqxmd.com/read/28804489/normalized-synergy-predicts-that-cd8-co-receptor-contribution-to-t-cell-receptor-tcr-and-pmhc-binding-decreases-as-tcr-affinity-increases-in-human-viral-specific-t-cells
#1
Chad M Williams, Alexandra A Schonnesen, Shu-Qi Zhang, Ke-Yue Ma, Chenfeng He, Tori Yamamoto, S Gail Eckhardt, Christopher A Klebanoff, Ning Jiang
The discovery of naturally occurring T cell receptors (TCRs) that confer specific, high-affinity recognition of pathogen and cancer-associated antigens remains a major goal in cellular immunotherapies. The contribution of the CD8 co-receptor to the interaction between the TCR and peptide-bound major histocompatibility complex (pMHC) has previously been correlated with the activation and responsiveness of CD8(+) T cells. However, these studies have been limited to model systems of genetically engineered hybridoma TCRs or transgenic mouse TCRs against either a single epitope or an array of altered peptide ligands...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28777668/therapeutic-tumor-control-of-her2-dna-vaccines-is-achieved-by-an-alteration-of-tumor-cells-and-tumor-microenvironment-by-gemcitabine-and-anti-gr-1-ab-treatment-in-a-her2-expressing-tumor-model
#2
Sayyed Nilofar Danishmalik, Jeong-Im Sin
Therapeutic control of tumors is challenging as they tend to alter their biological functions and microenvironment. In a CT26/HER2 tumor model, HER2 DNA vaccines and even anti-PD-L1 Abs failed to display antitumor therapeutic activity while inducing Ag-specific cytotoxic T lymphocyte (CTL) activity. To clarify this contradictory finding, we selected tumor cells (CT26/HER2-1) from one tumor-bearing animal in the therapeutic model. CT26/HER2-1 cells behaved similar to wild-type CT26/HER2 cells in their HER2 expression, immune cell stimulation for IFN-γ production, and antitumor immune sensitivity...
August 4, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28765875/quantum-dot-pmhc-multimers-vs-phycoerythrin-pmhc-tetramers-for-identification-of-hla-a-0201-restricted-phbv-core-antigen18-27-specific-t-cells
#3
Jianmeng Zhu, Yong Huang, Jing Su, Jian He, Yating Yu, Yongxiang Zhao, Xiaoling Lu
Detection of human leukocyte antigens-A2-restricted p-hepatitis B virus (HBV) core antigen‑specific cytotoxic T lymphocytes (CTLs) is important in the study of HBV immunopathogenesis and vaccine design. Currently, major histocompatibility complex (MHC) class I/peptide‑(p) MHCI tetramers are considered the optimal tools to detect antigen‑specific CTLs. However, the MHC‑tetramer technique also has certain drawbacks and is under continuous development. The quantum dot (QD) bioconjugates nanotechnology with its unique inorganic‑biological properties has been developing fast...
August 1, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28761354/pd-1-blockade-restores-impaired-function-of-ex-vivo-expanded-cd8-t-cells-and-enhances-apoptosis-in-mismatch-repair-deficient-epcam-pd-l1-cancer-cells
#4
Rajeev Kumar, Fang Yu, Yuan-Huan Zhen, Bo Li, Jun Wang, Yuan Yang, Hui-Xin Ge, Ping-Sheng Hu, Jin Xiu
BACKGROUND: Adoptive T cell therapy has been proven to be a promising modality for the treatment of cancer patients in recent years. However, the increased expression of inhibitory receptors could negatively regulate the function and persistence of transferred T cells which mediates T cell anergy, exhaustion, and tumor regression. In this study, we investigated increased cytotoxic activity after the blockade of PD-1 for effective immunotherapy. METHODS: The cytotoxic function of expanded CD8(+) CTLs and interactions with tumor cells investigated after blocking of PD-1...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28755872/new-approaches-for-the-enhancement-of-chimeric-antigen-receptors-for-the-treatment-of-hiv
#5
REVIEW
Mayra A Carrillo, Anjie Zhen, Jerome A Zack, Scott G Kitchen
HIV infection continues to be a life-long chronic disease in spite of the success of antiretroviral therapy (ART) in controlling viral replication and preventing disease progression. However, because of the high cost of treatment, severe side effects, and inefficiency in curing the disease with ART, there is a call for alternative therapies that will provide a functional cure for HIV. Cytotoxic T lymphocytes (CTLs) are vital in the control and clearance of viral infections and therefore immune-based therapies have attempted to engineer HIV-specific CTLs that would be able to clear the infection from the body...
July 14, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28751311/identification-of-a-novel-population-of-highly-cytotoxic-c-met-expressing-cd8-t-lymphocytes
#6
Mahdia Benkhoucha, Nicolas Molnarfi, Gürkan Kaya, Elodie Belnoue, Kristbjörg Bjarnadóttir, Pierre-Yves Dietrich, Paul R Walker, Denis Martinvalet, Madiha Derouazi, Patrice H Lalive
CD8(+) cytotoxic T lymphocytes (CTLs) are critical mediators of anti-tumor immunity, and controlling the mechanisms that govern CTL functions could be crucial for enhancing patient outcome. Previously, we reported that hepatocyte growth factor (HGF) limits effective murine CTL responses via antigen-presenting cells. Here, we show that a fraction of murine effector CTLs expresses the HGF receptor c-Met (c-Met(+) CTLs). Phenotypic and functional analysis of c-Met(+) CTLs reveals that they display enhanced cytolytic capacities compared to their c-Met(-) CTL counterparts...
July 27, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28747608/igg4-related-disease-mechanistic-insights-from-both-clinical-and-immunologic-understanding-of-this-condition
#7
Takashi Maehara
  IgG4-related disease (IgG4-RD) is a chronic inflammatory disease characterized by tumescent lesions with characteristic storiform fibrosis, obliterative phlebitis and a marked lymphoplasmacytic infiltrate that includes a large number of IgG4 positive plasma cells. It's widely accepted that rituximab-mediated B cell depletion therapy is effective for this disease. Important mechanistic insights correlated with the pathogenesis of IgG4-RD have been gradually disclosed from studies of patients treated by B cell depletion...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28746870/identification-of-a-genetic-variation-in-erap1-aminopeptidase-that-prevents-human-cytomegalovirus-mir-ul112-5p-mediated-immunoevasion
#8
Paolo Romania, Loredana Cifaldi, Benedetta Pignoloni, Nadia Starc, Valerio D'Alicandro, Ombretta Melaiu, Giuseppina Li Pira, Ezio Giorda, Rosalba Carrozzo, Monika Bergvall, Tomas Bergström, Lars Alfredsson, Tomas Olsson, Ingrid Kockum, Ilkka Seppälä, Terho Lehtimäki, Mikko A Hurme, Hartmut Hengel, Angela Santoni, Cristina Cerboni, Franco Locatelli, Mauro D'Amato, Doriana Fruci
Herein, we demonstrate that HCMV miR-UL112-5p targets ERAP1, thereby inhibiting the processing and presentation of the HCMV pp65495-503 peptide to specific CTLs. In addition, we show that the rs17481334 G variant, naturally occurring in the ERAP1 3' UTR, preserves ERAP1 from miR-UL112-5p-mediated degradation. Specifically, HCMV miR-UL112-5p binds the 3' UTR of ERAP1 A variant, but not the 3' UTR of ERAP1 G variant, and, accordingly, ERAP1 expression is reduced both at RNA and protein levels only in human fibroblasts homozygous for the A variant...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28743833/therapeutic-vaccine-to-cure-large-mouse-hepatocellular-carcinomas
#9
Zhen Han, De Yang, Anna Trivett, Joost J Oppenheim
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with limited therapeutic options. Here we report the development of a therapeutic vaccination regimen (shortened as 'TheraVac') consisting of intratumoral delivery of high-mobility group nucleosome-binding protein 1 (HMGN1), R848/resiquimod, and one of the checkpoint inhibitors (e.g. anti-CTLA4, anti-PD-L1, or low dose of Cytoxan). C57BL/6 mice harboring large (approximately 1 cm in diameter) established subcutaneous Hepa1-6 hepatomas were cured by intratumoral injections of TheraVac and became tumor-free long-term survivors...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28734174/old-and-new-adjuvants
#10
REVIEW
Amy S McKee, Philippa Marrack
Adjuvants have been deliberately added to vaccines since the 1920's when alum was discovered to boost antibody responses, leading to better protection. The first adjuvants were discovered by accident and were used in the safer but less immunogenic subunit vaccines, supposedly by providing an antigen depot to extend antigen presentation. Since that time, much has been discovered about how these adjuvants impact cells at the tissue site to activate innate immune responses, mobilize dendritic cells and drive adaptive immunity...
July 19, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28733529/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#11
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28724766/a-unique-t-cell-receptor-amino-acid-sequence-selected-by-htlv-i-tax301-309-specific-cytotoxic-t-cells-in-hla-a24-02-asymptomatic-carriers-and-adult-t-cell-leukemia-lymphoma-patients
#12
Yuko Ishihara, Yukie Tanaka, Seiichiro Kobayashi, Koji Kawamura, Hideki Nakasone, Ayumi Gomyo, Jin Hayakawa, Masaharu Tamaki, Yu Akahoshi, Naonori Harada, Machiko Kusuda, Kazuaki Kameda, Tomotaka Ugai, Hidenori Wada, Kana Sakamoto, Miki Sato, Kiriko Terasako-Saito, Misato Kikuchi, Shun-Ichi Kimura, Aki Tanihara, Shinichi Kako, Kaoru Uchimaru, Yoshinobu Kanda
We previously reported that the T-cell receptor (TCR) repertoire of HTLV-I Tax301-309-specific CD8(+) cytotoxic T-cells (Tax-CTLs) was highly restricted and a particular amino acid sequence motif, "PDR", was conserved among HLA-A*24:02(+) ATL patients who have undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR+CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-I. On the other hand, the TCR repertoires in Tax-CTL of asymptomatic HTLV-I carriers (ACs) remain unclear...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28720467/intradermal-immunization-with-raav1-vector-induces-robust-memory-cd8-t-cell-responses-independently-of-transgene-expression-in-dcs
#13
Alexandre Ghenassia, David-Alexandre Gross, Stéphanie Lorain, Fabiola Tros, Dominique Urbain, Sofia Benkhelifa-Ziyyat, Alain Charbit, Jean Davoust, Pascal Chappert
Recombinant adeno-associated viral (rAAV) vectors exhibit interesting properties as vaccine carriers for their ability to induce long-lasting antibody responses. However, rAAV-based vaccines have been suggested to trigger functionally impaired long-term memory CD8(+) T cell responses, in part due to poor dendritic cell (DC) transduction. Such results, albeit limited to intramuscular immunization, undermined the use of rAAV as vaccine vehicles against intracellular pathogens. We report here that intradermal immunization with a model rAAV2/1-based vaccine drives the development of bona fide long-term memory CD8(+) T cell responses...
July 15, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28716933/cortical-actin-recovery-at-the-immunological-synapse-leads-to-termination-of-lytic-granule-secretion-in-cytotoxic-t-lymphocytes
#14
Alex T Ritter, Senta M Kapnick, Sricharan Murugesan, Pamela L Schwartzberg, Gillian M Griffiths, Jennifer Lippincott-Schwartz
CD8(+) cytotoxic T lymphocytes (CTLs) eliminate virally infected cells through directed secretion of specialized lytic granules. Because a single CTL can kill multiple targets, degranulation must be tightly regulated. However, how CTLs regulate the termination of granule secretion remains unclear. Previous work demonstrated that centralized actin reduction at the immune synapse precedes degranulation. Using a combination of live confocal, total internal reflection fluorescence, and superresolution microscopy, we now show that, after granule fusion, actin recovers at the synapse and no further secretion is observed...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28715455/synthetic-melanin-bound-to-subunit-vaccine-antigens-significantly-enhances-cd8-t-cell-responses
#15
Antoine F Carpentier, Frédéric Geinguenaud, Thi Tran, Floraly Sejalon, Antoine Martin, Laurence Motte, Eric Tartour, Claire Banissi
Cytotoxic T-lymphocytes (CTLs) play a key role in immunity against cancer; however, the induction of CTL responses with currently available vaccines remains difficult. Because several reports have suggested that pigmentation and immunity might be functionally linked, we investigated whether melanin can act as an adjuvant in vaccines. Short synthetic peptides (8-35 amino acids long) containing T-cell epitopes were mixed with a solution of L-Dopa, a precursor of melanin. The mixture was then oxidized to generate nanoparticles of melanin-bound peptides...
2017: PloS One
https://www.readbyqxmd.com/read/28713366/intratumoral-lentivector-mediated-tgf-%C3%AE-1-gene-downregulation-as-a-potent-strategy-for-enhancing-the-antitumor-effect-of-therapy-composed-of-cyclophosphamide-and-dendritic-cells
#16
Joanna Rossowska, Natalia Anger, Agnieszka Szczygieł, Jagoda Mierzejewska, Elżbieta Pajtasz-Piasecka
Vaccination with dendritic cells (DCs) stimulated with tumor antigens can induce specific cellular immune response that recognizes a high spectrum of tumor antigens. However, the ability of cancer cells to produce immunosuppressive factors drastically decreases the antitumor activity of DCs. The main purpose of the study was to improve the effectiveness of DC-based immunotherapy or chemoimmunotherapy composed of cyclophosphamide (CY) and DCs by application of lentivectors (LVs)-encoding short hairpin RNA specific for TGF-β1 (shTGFβ1 LVs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28706421/gastric-cancer-derived-heat-shock-protein-gp96-peptide-complex-enhances-dendritic-cell-activation
#17
Wen-Wen Lu, Hong Zhang, You-Ming Li, Feng Ji
AIM: To investigate the role of heat shock protein (HSP)-glycoprotein (gp)96 in dendritic cells (DCs) and lymphocytes induction in gastric cancer (GC). METHODS: Human GC cell lines KATOIII, MKN-28 and SGC-7901 were infected with adenovirus gp96 at a multiplicity of infection of 100. gp96-GC antigen peptide complexes were purified. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, lactate dehydrogenase (LDH) release assay and enzyme-linked immunosorbent assay were used to determine allo-reactive T cell stimulation, natural killer (NK) cell activity and expression of cytokines (such as interleukin (IL)-10, IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α), respectively...
June 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28699227/implication-of-chemo-resistant-memory-t-cells-for-immune-surveillance-in-patients-with-sarcoma-receiving-chemotherapy
#18
Yuji Shibayama, Tomohide Tsukahara, Makoto Emori, Kenji Murata, Emi Mizushima, Yoshihiko Hirohashi, Takayuki Kanaseki, Munehide Nakatsugawa, Terufumi Kubo, Toshihiko Yamashita, Noriyuki Sato, Toshihiko Torigoe
Chemotherapy has improved the prognosis of patients with sarcomas. However, it may suppress anti-tumor immunity. Recently, we reported a novel CD8(+) memory T cell population with a chemo-resistance property, "young memory" T (TYM ) cells. In this study, we investigated the proportion and function of TYM cells in peripheral blood of healthy donors and sarcoma patients who received chemotherapy and those who did not. The proportion of TYM cells was significantly decreased in patients compared with that in healthy donors...
July 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28697053/postoperative-adjuvant-therapy-for-resectable-pancreatic-cancer-with-gemcitabine-and-adoptive-immunotherapy
#19
Hiroto Matsui, Shoichi Hazama, Kazuhiko Sakamoto, Yoshitaro Shindo, Shinsuke Kanekiyo, Masao Nakashima, Satoshi Matsukuma, Yoshihiro Tokuhisa, Michihisa Iida, Nobuaki Suzuki, Kiyoshi Yoshimura, Shigeru Takeda, Tomio Ueno, Shigefumi Yoshino, Masaaki Oka, Hiroaki Nagano
OBJECTIVES: We previously described adoptive immunotherapy (AIT) with cytotoxic T lymphocytes (CTLs) stimulated by the mucin 1 (MUC1)-expressing human pancreatic cancer cell line YPK-1 (MUC1-CTLs) and demonstrated that MUC1-CTLs might prevent liver metastasis. In the present study, we combined gemcitabine (GEM) and AIT for the treatment of pancreatic cancer. METHODS: A total of 43 patients who underwent radical pancreatectomy received treatment with MUC1-CTLs and GEM...
July 11, 2017: Pancreas
https://www.readbyqxmd.com/read/28690108/improving-homing-in-t-cell-therapy
#20
Debora Vignali, Marinos Kallikourdis
Cytotoxic T lymphocytes (cytotoxic T cells, CTLs) are an immune effector cell population that can mediate specific immune responses against cancer. Based on this concept, tumor immunotherapy protocols have been developed using adoptive transfer of in vitro-expanded autologous T cells that can kill cancer cells. However, fully functional adoptive T cell therapies (ACT) are hampered by the inability to guarantee that all transferred T cells manage to reach the tumor sites and make contact with cancer cells. The lack of tumor homing of T cells may be caused by a variety of reasons...
June 23, 2017: Cytokine & Growth Factor Reviews
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