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Cytotoxic t lymphocytes

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https://www.readbyqxmd.com/read/29140111/purging-exhausted-virus-specific-cd8-t-cell-phenotypes-by-somatic-cell-reprogramming
#1
Joshua Chan, Patrick Y Kim, Emiko Kranz, Yoshiko Nagaoka, YooJin Lee, Jing Wen, Heidi J Elsaesser, Meng Qin, David G Brooks, Gene-Errol Ringpis, Irvin S Y Chen, Masakazu Kamata
Cytotoxic T cells are critical in controlling virus infections. However, continuous antigen stimulation and negative regulatory factors cause CD8 T cells to enter a dysfunctional state (T cell exhaustion), resulting in viral persistence. We hypothesized that the exhausted T cell state could be molecularly rejuvenated using a somatic cell reprogramming technology, which is technically able to convert any types of cells to induced pluripotent stem cells (iPSCs), to regenerate functional T cells capable of purging chronic infection...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29139554/immune-checkpoint-inhibitors-new-strategies-to-checkmate-cancer
#2
REVIEW
Ruairi A M Wilson, T R Jeffry Evans, Alasdair R Fraser, Robert J B Nibbs
Immune checkpoint inhibitors (ICIs) targeting Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4) or Programmed cell Death protein 1 (PD-1) receptors have demonstrated remarkable efficacy in subsets of patients with malignant disease. This emerging treatment modality holds great promise for future cancer treatment and has engaged pharmaceutical research interests in tumour immunology. While ICIs can induce rapid and durable responses in some patients, identifying predictive factors for effective clinical responses has proven challenging...
November 15, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29138980/cd28-neg-t-lymphocytes-of-a-melanoma-patient-harbor-tumor-immunity-and-a-high-frequency-of-germline-encoded-and-public-tcrs
#3
Hisayoshi Hashimoto, Marco Sterk, Karin Schilbach
Increased numbers of CD8(+)CD28(neg.) T cells have been detected in the peripheral blood of patients with several types of malignancies. However, the role of these cells in anticancer immunity are not yet clear and CD8(+)CD28(neg.) T cells are a controversially discussed subpopulation reported both as immunosuppressive and cytotoxic. In this study, we examined the T cell receptor (TCR) repertoire and complementarity-determining region 3 sequences of CD28(neg.) T cells in a melanoma patient with recurrent disease who achieved long-term disease-free status...
November 14, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29138342/immunotherapy-of-hepatocellular-carcinoma-facts-and-hopes
#4
Mercedes Iñarrairaegui, Ignacio Melero, Bruno Sangro
Treatment of patients with hepatocellular carcinoma in the advanced stage remains a great challenge, with very few drugs approved. After decades of failures of immune therapies, immune checkpoint inhibitors have emerged as potentially effective treatments for patients with hepatocellular carcinoma in the advanced stage. Immune checkpoints, including human cancer, cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), are surface proteins expressed in a variety of immune cells, and mostly provide immunosuppressive signals...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29137359/granulysin-expressed-in-a-humanized-mouse-model-induces-apoptotic-cell-death-and-suppresses-tumorigenicity
#5
Ya-Wen Hsiao, Tsung-Ching Lai, Yu-Hsiang Lin, Chia-Yi Su, Jih-Jong Lee, Albert Taiching Liao, Yuan-Feng Lin, Shu-Chen Hsieh, Alexander T H Wu, Michael Hsiao
Granulysin (GNLY) is a cytolytic and proinflammatory protein expressed in activated human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Conventional mouse models cannot adequately address the triggering mechanism and immunopathological pathways in GNLY-associated diseases due to lack of the GNLY gene in the mouse genome. Therefore, we generated a humanized immune system (HIS) mouse model by transplanting human umbilical cord blood mononuclear cells into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl) /SzJ (NSG) mice after sublethally irradiation...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135922/targeting-immune-cell-checkpoints-during-sepsis
#6
REVIEW
Naeem K Patil, Yin Guo, Liming Luan, Edward R Sherwood
Immunosuppression is increasingly being recognized as one of the causes of increased morbidity and mortality during sepsis. Both innate and adaptive immune system dysfunction have been shown to cause an impaired ability to eradicate the primary infection and also lead to frequent occurrence of secondary opportunistic infections. Pre-clinical and clinical studies have shown that inhibitory immune checkpoint molecules, including programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), T cell membrane protein-3 (TIM-3), Lymphocyte activation-gene-3 (LAG-3) and 2B4, are upregulated during the course of sepsis...
November 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29135371/follistatin-like-protein-1-upregulates-dendritic-cell-based-immunity-in-patients-with-nasopharyngeal-carcinoma
#7
Hong Wang, Shiping Huang, Senyong Wu, Shaolin Yin, Anzhou Tang, Wensheng Wen
Follistatin-like protein-1 (FSTL1) is an inflammatory factor that can induce an inflammatory response and is expressed in cancers. However, little is known about its content and function in nasopharyngeal carcinoma (NPC). Interleukin (IL)-12 and IL-4 are primarily secreted by dendritic cells (DCs) and activated T lymphocytes, respectively; these factors can induce Th cell differentiation and cytotoxic lymphocyte production, both of which facilitate tumors through the STAT4 and STAT6 pathways, respectively. In this study, the relationship between FSTL1 and both IL-12 and IL-4 as well as the functional mechanism of these cytokines was explored...
November 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29133939/precision-medicine-for-urothelial-bladder-cancer-update-on-tumour-genomics-and-immunotherapy
#8
REVIEW
Kenneth M Felsenstein, Dan Theodorescu
Effective management of advanced urothelial bladder cancer is challenging. New discoveries that improve our understanding of molecular bladder cancer subtypes have revealed numerous potentially targetable genomic alterations and demonstrated the efficacy of treatments that harness the immune system. These findings have begun to change paradigms of bladder cancer therapy. For example, DNA repair pathway mutations in genes such as ERCC2, FANCC, ATM, RB1, and others can predict responses to neoadjuvant platinum-based chemotherapies and to targeted therapies on the basis of mutation status...
November 14, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29131040/adverse-reactions-to-biologics-melanoma-ipilimumab-nivolumab-pembrolizumab
#9
Shelley Ji Eun Hwang, Pablo Fernández-Peñas
With increasing use of immunotherapies such as anti-cytotoxic T cell lymphocyte antigen-4 and anti-programmed cell death 1 antibodies, various skin toxicities have emerged. Severity of skin toxicities varies from mild lichenoid reaction to severe toxic epidermal necrolysis. Appropriate diagnosis and management of these skin toxicities are essential for optimal patient care and to avoid unnecessary cessation of anti-cancer therapies. This review summarises a wide range of cutaneous manifestations associated with immunotherapy usage in patients with metastatic melanoma...
2018: Current Problems in Dermatology
https://www.readbyqxmd.com/read/29130994/enhancement-of-anti-leukemia-immunity-by-leukemia-derived-exosomes-via-downregulation-of-tgf-%C3%AE-1-expression
#10
Fang Huang, Jiangbo Wan, Weiwei Hu, Siguo Hao
BACKGROUND/AIMS: Minimal residual leukemia cells (MRLs) are difficult to eradicate through traditional treatment and therefore remain to be a major threat to the long-term survival of leukemia patients. Tumor-derived exosomes (TEXs), which carry tumor associated antigens (TAA), may be a potential cell-free tumor vaccine for the specific eradication of MRLs. However, TEXs are intended to be less immunogenic due to exosomal TGF-β1. To further optimize the efficacy of TEX-based vaccines, we investigated whether exosomes from TGF-β1 silenced leukemia cells (LEXTGF-β1si) had an increased potential to induce a specific antitumor effect compared with non-modified exosomes...
November 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29129674/cytotoxic-t-lymphocyte-granzyme-b-mediates-neuronal-cell-death-during-plasmodium-berghei-anka-induced-experimental-cerebral-malaria
#11
Prabhakar Eeka, Prakash Babu Phanithi
Cerebral malaria is a complex, acute, neurological disease characterised by a sudden onset of cerebral symptoms. This disease is manifested as initial arousable stage that is followed by an unarousable coma and eventually death. Parasite burden and CD8+ T cell count in the brain determines the disease outcome. Cytotoxic CD8+ T cell-derived Granzyme-b is required for the development of experimental cerebral malaria (ECM), but the mechanism of pathogenesis is not known. Here, we show that CD8+ T cells infiltrate in to the brain during ECM releasing Granzyme-b that is cytotoxic to neuronal cells...
November 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29129094/rational-combination-of-immunotherapy-for-triple-negative-breast-cancer-treatment
#12
Chia-Wei Li, Seung-Oe Lim, Jennifer L Hsu, Mien-Chie Hung
Recent evidence indicates that tumor infiltrating lymphocytes (TILs), including cytotoxic T cells, are present in the tumor microenvironment of triple-negative breast cancers (TNBC). Despite the presence of cytotoxic T cells, these tumors still develop, progress, and metastasize, suggesting evasion of immune response. One mechanism of immunosuppression is the presence of the T cell inhibitory molecule, programmed death protein 1 (PD-1), on infiltrating T cells and its cognate ligand programmed death ligand 1 (PD-L1) on tumor cells, myeloid dendritic cells (DCs), and macrophages, in the tumor microenvironment...
October 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29129093/xxxxx
#13
Tomas G Lyons, Geoffrey Y Ku
The poor prognosis for patients with esophagogastric cancers (EGC) requires the development of newer more effective therapies to further improve the treatment outcomes for this disease. Immunotherapy is a novel treatment strategy that is dramatically changing the treatment landscape for several types of cancers. Cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death the programmed death (PD)-1/PD-ligand are essential immune checkpoint inhibitors that suppress T cell activation. Targeting of these immune checkpoints with monoclonal antibodies has shown clinical efficacy in several solid tumors which has led to their approval and use in routine clinical practice...
October 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29128969/in-vasculitis-of-small-muscular-arteries-activation-of-vessel-infiltrating-cd8-t-cells-seems-to-be-antigen-independent
#14
Mikiko Kobayashi, Eisaku Ogawa, Ryuhei Okuyama, Hiroyuki Kanno
The etiology of polyarteritis nodosa (PAN) and localized PAN is still unknown, although a T cell-mediated immune mechanism has been considered. CD8 T cells participate not only in the antigen-dependent adaptive immune system, but also in the antigen-independent innate immune system. Non-antigen-activated CD8 T cells express a unique phenotype: granzyme B (GrB) positive /CD25 negative /programmed death-1 (PD-1) negative. The aims of this study were to assess the participation of T cells, especially innate CD8 T cells, in the development of vasculitis...
November 11, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29128025/posttransplant-lymphoproliferative-disorder-in-solid-organ-and-hematopoietic-stem-cell-transplantation
#15
REVIEW
Sarah J Nagle, Ran Reshef, Donald E Tsai
Posttransplant lymphoproliferative disorders (PTLD) represent an immunosuppression-related lymphoid or plasmacytic proliferation that occur in the setting of solid organ transplant or allogeneic hematopoietic stem cell transplantation (HSCT). PTLD is a devastating consequence of HSCT and solid organ transplantation with a high morbidity and mortality. Most commonly, PTLD is related to Epstein-Barr virus (EBV) infection, but an increasing number of non-EBV-related cases are occurring. Initial therapy involves withdrawal of immunosuppression with or without antibody or cytotoxic chemotherapy...
December 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/29127433/targeting-and-suppression-of-her3-positive-breast-cancer-by-t-lymphocytes-expressing-a-heregulin-chimeric-antigen-receptor
#16
Bai-Le Zuo, Bo Yan, Guo-Xu Zheng, Wen-Jin Xi, Xiao Zhang, An-Gang Yang, Lin-Tao Jia
Chimeric antigen receptor-modulated T lymphocytes (CAR-T) have emerged as a powerful tool for arousing anticancer immunity. Endogenous ligands for tumor antigen may outperform single-chain variable fragments to serve as a component of CARs with high cancer recognition efficacy and minimized immunogenicity. As heterodimerization and signaling partners for human epidermal growth factor receptor 2 (HER2), HER3/HER4 has been implicated in tumorigenic signaling and therapeutic resistance of breast cancer. In this study, we engineered T cells with a CAR consisting of the extracellular domain of heregulin-1β (HRG1β) that is a natural ligand for HER3/HER4, and evaluated the specific cytotoxicity of these CAR-T cells in cultured HER3 positive breast cancer cells and xenograft tumors...
November 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29123959/immunological-efficacy-of-glypican-3-peptide-vaccine-in-patients-with-advanced-hepatocellular-carcinoma
#17
Nobuhiro Tsuchiya, Toshiaki Yoshikawa, Norihiro Fujinami, Keigo Saito, Shoichi Mizuno, Yu Sawada, Itaru Endo, Tetsuya Nakatsura
We have previously conducted a phase I trial to test the efficacy of a glypican-3 (GPC3) peptide vaccine in patients with advanced hepatocellular carcinoma (HCC); however, its immunological mechanism of action remains unclear. Here, we report a pilot study conducted to evaluate the immunological mechanisms of action of this GPC3 peptide vaccine (UMIN-CTR number 000005093). Eleven patients with advanced HCC were vaccinated with the GPC3 peptide in this trial. The primary end point was GPC3 peptide-specific immune response induced by the GPC3 peptide vaccination...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123946/tumor-cell-death-by-pattern-sensing-of-exogenous-rna-tumor-cell-tlr3-directly-induces-necroptosis-by-poly-i-c-in-vivo-independent-of-immune-effector-mediated-tumor-shrinkage
#18
Hiromi Takaki, Hiroaki Shime, Misako Matsumoto, Tsukasa Seya
Poly(I:C) acts on dendritic cells to induce potent antitumor effects through the production of cytokines/interferons, activation of natural killer cells and proliferation of cytotoxic T lymphocytes. In some tumor or myeloid lineages, poly(I:C) seemed to induce necroptosis in concert with a pan-caspase inhibitor by directly acting on toll-like receptor (TLR) 3 in both in vivo and in vitro models.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29122114/frequency-and-perforin-expression-of-different-lymphocyte-subpopulations-in-patients-with-lower-limb-fracture-and-thoracic-injury
#19
Nikola Grzalja, Tedi Cicvaric, Danijel Knezevic, Janja Kuharic, Alan Sustic, Bore Bakota, Simona Komen, Vlatka Sotosek Tokmadzic
INTRODUCTION: Trauma with multiple injuries is associated with a high risk of complications, which may be related to excessive stimulation of inflammatory and anti-inflammatory responses. Although the effects of polytrauma on the immune response have been well established at the cellular and molecular levels, there is little information about the changes in the cytolytic potential of immunocompetent cells, including expression of cytotoxic molecules such as perforin. Therefore, the objective of the present study was to analyse and compare differences in the frequency and perforin expression of leukocyte subpopulations in the peripheral blood of patients with lower limb fracture, thoracic injury, and simultaneous lower limb fracture and thoracic injury...
November 2017: Injury
https://www.readbyqxmd.com/read/29120583/role-of-lymphocyte-subpopulations-in-the-immunopathogenesis-of-psoriasis-and-the-effect-of-narrow-band-uvb-phototherapy-on-the-immunological-profile-of-psoriasis-patients
#20
Mona Fattouh, Asmaa N El-Din, Mohammed A El-Hamd
Psoriasis is one of the most common chronic, inflammatory, T-cell-mediated autoimmune diseases. Narrow-band UVB (NB-UVB) therapy is widely used in the treatment of psoriasis; however, its mechanism of action is still not well understood. The objective of this study was to investigate the circulating T-lymphocyte subpopulations in psoriasis patients before and after NB-UVB, to get insights into the mechanism of NB-UVB in the treatment of psoriasis. The severity of psoriasis was assessed by means of the Psoriasis Area and Severity Index (PASI-score)...
January 2017: Egyptian Journal of Immunology
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