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PD-1 T cell

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https://www.readbyqxmd.com/read/29052782/clinical-and-immunologic-evaluation-of-three-metastatic-melanoma-patients-treated-with-autologous-melanoma-reactive-tcr-transduced-t-cells
#1
Tamson Moore, Courtney Regan Wagner, Gina M Scurti, Kelli A Hutchens, Constantine Godellas, Ann Lau Clark, Elizabeth Motunrayo Kolawole, Lance M Hellman, Nishant K Singh, Fernando A Huyke, Siao-Yi Wang, Kelly M Calabrese, Heather D Embree, Rimas Orentas, Keisuke Shirai, Emilia Dellacecca, Elizabeth Garrett-Mayer, Mingli Li, Jonathan M Eby, Patrick J Stiff, Brian D Evavold, Brian M Baker, I Caroline Le Poole, Boro Dropulic, Joseph I Clark, Michael I Nishimura
Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4(+) and CD8(+) T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4(+) and CD8(+) T cells...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29051561/magt1-mediated-disturbance-of-mg-2-homeostasis-lead-to-exhausted-of-hbv-infected-nk-and-cd8-t-cells
#2
Bo Diao, Xiaoyong Huang, Shen Guo, Chengying Yang, Guosong Liu, Yongwen Chen, Yuzhang Wu
The magnesium transporter 1 (MAGT1) is a critical regulator of basal intracellular free magnesium ([Mg(2+)]i) levels. It has been shown that MAGT1 was involved in the disorder in Mg(2+) homeostasis after Epstein-Barr virus (EBV) infection. Here, we identified the effects of MAGT1-mediated disturbance of Mg(2+) homeostasis on chronic hepatitis B virus (HBV)-infected natural killer (NK) and CD8(+) T cells. The expression of MAGT1 was gradually decreased with the increase of infected time in CD8(+) T cells, but not with that in NK cells, of the patients...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051270/hypoxia-induced-pd-l1-pd-1-crosstalk-impairs-t-cell-function-in-sleep-apnoea
#3
Carolina Cubillos-Zapata, Jose Avendaño-Ortiz, Enrique Hernandez-Jimenez, Victor Toledano, Jose Casas-Martin, Anibal Varela-Serrano, Marta Torres, Isaac Almendros, Raquel Casitas, Isabel Fernández-Navarro, Aldara Garcia-Sanchez, Luis A Aguirre, Ramón Farre, Eduardo López-Collazo, Francisco García-Rio
Obstructive sleep apnoea (OSA) is associated with higher cancer incidence, tumour aggressiveness and cancer mortality, as well as greater severity of infections, which have been attributed to an immune deregulation. We studied the expression of programmed cell death (PD)-1 receptor and its ligand (PD-L1) on immune cells from patients with OSA, and its consequences on immune-suppressing activity. We report that PD-L1 was overexpressed on monocytes and PD-1 was overexpressed on CD8(+) T-cells in a severity-dependent manner...
October 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29050367/expression-and-clinical-association-of-programmed-cell-death-1-programmed-death-ligand-1-and-cd8-lymphocytes-in-primary-sarcomas-is-subtype-dependent
#4
Anke E M van Erp, Yvonne M H Versleijen-Jonkers, Melissa H S Hillebrandt-Roeffen, Laurens van Houdt, Mark A J Gorris, Laura S van Dam, Thomas Mentzel, Marije E Weidema, C Dilara Savci-Heijink, Ingrid M E Desar, Hans H M Merks, Max M van Noesel, Janet Shipley, Winette T A van der Graaf, Uta E Flucke, Friederike A G Meyer-Wentrup
In order to explore the potential of immune checkpoint blockade in sarcoma, we investigated expression and clinical relevance of programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1) and CD8 in tumors of 208 sarcoma patients. Primary untreated osteosarcoma (n = 46), Ewing sarcoma (n = 32), alveolar rhabdomyosarcoma (n = 20), embryonal rhabdomyosarcoma (n = 77), synovial sarcoma (n = 22) and desmoplastic small round cell tumors (DSRCT) (n = 11) were examined immunohistochemically. PD-L1 expression was predominantly detected in alveolar and embryonal rhabdomyosarcomas (15% and 16%, respectively)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050282/effective-antitumor-peptide-vaccines-can-induce-severe-autoimmune-pathology
#5
Hussein Sultan, Jimena Trillo-Tinoco, Paulo Rodriguez, Esteban Celis
Immunotherapy has shown a tremendous success in treating cancer. Unfortunately, this success is frequently associated with severe autoimmune pathology. In this study, we used the transgenic RIP-gp mouse model to assess the antitumor therapeutic benefit of peptide vaccination while evaluating the possible associated autoimmune pathology. We report that palmitoylated gp33-41 peptide and poly-IC adjuvant vaccine (BiVax) generated ∼ 5-10 % of antigen specific T cell responses in wild type and supposedly immune tolerant RIP-gp mice...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048372/%C3%AE-synuclein-regulates-neuronal-cholesterol-efflux
#6
Jen-Hsiang T Hsiao, Glenda M Halliday, Woojin Scott Kim
α-Synuclein is a neuronal protein that is at the center of focus in understanding the etiology of a group of neurodegenerative diseases called α-synucleinopathies, which includes Parkinson's disease (PD). Despite much research, the exact physiological function of α-synuclein is still unclear. α-Synuclein has similar biophysical properties as apolipoproteins and other lipid-binding proteins and has a high affinity for cholesterol. These properties suggest a possible role for α-synuclein as a lipid acceptor mediating cholesterol efflux (the process of removing cholesterol out of cells)...
October 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29046141/generation-and-characterization-of-a-bispecific-antibody-targeting-both-pd-1-and-c-met
#7
Yi Wu, Min Yu, Zujun Sun, Weihua Hou, Yuxiong Wang, Qingyun Yuan, Wei Mo
Bispecific antibodies, BsAbs, are molecules with the ability to bind to two different epitopes on the same or different antigens. The goal of this study was to create a novel bispecific antibody targeting both cellular-mesenchymal to epithelial transition factor(c-MET) and programmed death-1(PD-1) as an anti-cancer therapeutic candidate. Upon binding to the c-MET antigen on a tumor cell and the PD-1 antigen on a T cell, a BsAb can redirect T cells for tumor killing. Based on the original sequences of PD-1 and c-MET mAbs, a BsAb gene was designed, and cloned into the pCEP4 vector...
October 17, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/29045906/ctla-4-pd-1-memory-cd4-t-cells-critically-contribute-to-viral-persistence-in-antiretroviral-therapy-suppressed-siv-infected-rhesus-macaques
#8
Colleen S McGary, Claire Deleage, Justin Harper, Luca Micci, Susan P Ribeiro, Sara Paganini, Leticia Kuri-Cervantes, Clarisse Benne, Emily S Ryan, Robert Balderas, Sherrie Jean, Kirk Easley, Vincent Marconi, Guido Silvestri, Jacob D Estes, Rafick-Pierre Sekaly, Mirko Paiardini
Antiretroviral therapy (ART) suppresses viral replication in HIV-infected individuals but does not eliminate the reservoir of latently infected cells. Recent work identified PD-1(+) follicular helper T (Tfh) cells as an important cellular compartment for viral persistence. Here, using ART-treated, SIV-infected rhesus macaques, we show that CTLA-4(+)PD-1(-) memory CD4(+) T cells, which share phenotypic markers with regulatory T cells, were enriched in SIV DNA in blood, lymph nodes (LN), spleen, and gut, and contained replication-competent and infectious virus...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045749/immune-checkpoint-inhibitor-related-myocarditis
#9
Kazuko Tajiri, Kazutaka Aonuma, Ikuo Sekine
Immune checkpoint inhibitors have demonstrated significant clinical benefit in many cancers. The clinical benefit afforded by these treatments can be accompanied by a unique and distinct spectrum of adverse events. Recently, several fatal cases of immune checkpoint inhibitor-related myocarditis were reported. Although its frequency is comparatively lower than that of other immune-related adverse events, myocarditis can lead to circulatory collapse and lethal ventricular arrhythmia. Immune checkpoints, cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), play important roles in establishing peripheral tolerance to the heart...
October 17, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29045526/lag-3-tumor-infiltrating-lymphocytes-in-breast-cancer-clinical-correlates-and-association-with-pd-1-pd-l1-tumors
#10
S Burugu, D Gao, S Leung, S K Chia, T O Nielsen
BACKGROUND: Novel immune checkpoint blockade strategies are being evaluated in clinical trials and include targeting the lymphocyte activation gene 3 (LAG-3) checkpoint, alone or in combination with PD-1/PD-L1 blockade. We investigated LAG-3 expression and its prognostic value in a large series of breast cancer patients, and correlated LAG-3 expression with key biomarkers including PD-1 and PD-L1. EXPERIMENTAL DESIGN: LAG-3 expression was evaluated by immunohistochemistry (IHC) on two tissue microarray series incorporating 4322 breast cancer primary excision specimens (N=330 in the training and N= 3,992 in the validation set) linked to detailed clinico-pathological, biomarker and long term clinical outcome data...
September 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045188/rapid-evolution-of-thyroid-dysfunction-in-patients-treated-with-nivolumab
#11
Grenye O'Malley, Hanna J Lee, Samir Parekh, Matthew D Galsky, Cardinale B Smith, Philip Friedlander, Robert T Yanagisawa, Emily J Gallagher
OBJECTIVE: To describe the evolution of thyroid dysfunction in a series of patients with cancer treated with the immune checkpoint inhibitor anti-programmed cell death protein-1 (PD-1) monoclonal antibody, nivolumab. METHODS: Cases of thyroid dysfunction after initiation of checkpoint inhibitor treatment were identified from the Division of Endocrinology clinical practice at Mount Sinai Hospital, New York from April 2016 to February 2017. Charts were reviewed to identify patients treated with nivolumab with new onset of thyroid dysfunction...
October 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29044503/clinical-significance-of-programmed-cell-death-ligand-1-expression-and-the-immune-microenvironment-at-the-invasive-front-of-colorectal-cancers-with-high-microsatellite-instability
#12
Shotaro Korehisa, Eiji Oki, Makoto Iimori, Yu Nakaji, Mototsugu Shimokawa, Hiroshi Saeki, Shinji Okano, Yoshinao Oda, Yoshihiko Maehara
Immunotherapy is reportedly effective in colorectal cancers (CRCs) with high microsatellite instability (MSI-H); however, the specific cell types that respond to immune checkpoint therapy are unclear. Herein, we aimed to examine the expression of programmed cell death-ligand 1 (PD-L1) and related proteins in MSI-H and microsatellite-stable (MSS) CRCs to investigate the immune microenvironment at the tumor's invasive front. The MSI status was retrospectively assessed in 499 patients undergoing surgical resection of primary CRC; of these, 48 were classified as MSI-H...
October 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29042640/validation-of-multiplex-immunofluorescence-panels-using-multispectral-microscopy-for-immune-profiling-of-formalin-fixed-and-paraffin-embedded-human-tumor-tissues
#13
Edwin R Parra, Naohiro Uraoka, Mei Jiang, Pamela Cook, Don Gibbons, Marie-Andrée Forget, Chantale Bernatchez, Cara Haymaker, Ignacio I Wistuba, Jaime Rodriguez-Canales
Immune-profiling is becoming an important tool to identify predictive markers for the response to immunotherapy. Our goal was to validate multiplex immunofluorescence (mIF) panels to apply to formalin-fixed and paraffin-embedded tissues using a set of immune marker antibodies, with the Opal™ 7 color Kit (PerkinElmer) in the same tissue section. We validated and we described two panels aiming to characterize the expression of PD-L1, PD-1, and subsets of tumor associated immune cells. Panel 1 included pancytokeratin (AE1/AE3), PD-L1, CD4, CD8, CD3, CD68, and DAPI, and Panel 2 included pancytokeratin, PD-1, CD45RO, granzyme B, CD57, FOXP3, and DAPI...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29042512/in-vitro-reconstitution-of-t-cell-receptor-mediated-segregation-of-the-cd45-phosphatase
#14
Catherine B Carbone, Nadja Kern, Ricardo A Fernandes, Enfu Hui, Xiaolei Su, K Christopher Garcia, Ronald D Vale
T cell signaling initiates upon the binding of peptide-loaded MHC (pMHC) on an antigen-presenting cell to the T cell receptor (TCR) on a T cell. TCR phosphorylation in response to pMHC binding is accompanied by segregation of the transmembrane phosphatase CD45 away from TCR-pMHC complexes. The kinetic segregation hypothesis proposes that CD45 exclusion shifts the local kinase-phosphatase balance to favor TCR phosphorylation. Spatial partitioning may arise from the size difference between the large CD45 extracellular domain and the smaller TCR-pMHC complex, although parsing potential contributions of extracellular protein size, actin activity, and lipid domains is difficult in living cells...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29042417/restoration-of-natural-killer-cell-anti-metastatic-activity-by-il-12-and-checkpoint-blockade
#15
Isabel Ohs, Laura Ducimetiere, Joana Marinho, Paulina Kulig, Burkhard Becher, Sonia Tugues
Immune checkpoint therapies target tumor antigen-specific T cells, but less is known about their effects on natural killer (NK) cells, which help control metastasis. In studying the development of lung metastases, we found that NK cells lose their cytotoxic capacity and acquire a molecular signature defined by the expression of co-inhibitory receptors. In an effort to overcome this suppressive mechanism, we evaluated NK cell responses to the immunostimulatory cytokine IL-12. Exposure to IL-12 rescued the cytotoxicity of NK cells but also led to the emergence of an immature NK cell population which expressed high levels of the co-inhibitory molecules PD-1, Lag-3 and TIGIT, thereby limiting NK cell-mediated control of pulmonary metastases...
October 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/29038297/tumor-pdcd1lg2-pd-l2-expression-and-the-lymphocytic-reaction-to-colorectal-cancer
#16
Yohei Masugi, Reiko Nishihara, Tsuyoshi Hamada, Mingyang Song, Annacarolina da Silva, Keisuke Kosumi, Mancang Gu, Yan Shi, Wanwan Li, Li Liu, Daniel Nevo, Kentaro Inamura, Yin Cao, Xiaoyun Liao, Katsuhiko Nosho, Andrew T Chan, Marios Giannakis, Adam J Bass, F Stephen Hodi, Gordon J Freeman, Scott J Rodig, Charles S Fuchs, Zhi Rong Qian, Jonathan A Nowak, Shuji Ogino
Expression of the immune-checkpoint ligand CD274 (programmed cell death 1 ligand 1, PD-L1, from gene CD274) contributes to suppression of antitumor T cell-mediated immune response in various tumor types. However, the role of PDCD1LG2 (PD-L2, CD273, from gene PDCD1LG2) in the tumor microenvironment remains unclear. We hypothesized that tumor PDCD1LG2 expression might be inversely associated with lymphocytic reactions to colorectal cancer. We examined tumor PDCD1LG2 expression by immunohistochemistry in 823 colon and rectal carcinoma cases within two U...
October 16, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29038249/anti-pd-1-antibody-treatment-promotes-clearance-of-persistent-cryptococcal-lung-infection-in-mice
#17
Jonathan A Roussey, Steven P Viglianti, Seagal Teitz-Tennenbaum, Michal A Olszewski, John J Osterholzer
Activation of immunomodulatory pathways in response to invasive fungi can impair clearance and promote persistent infections. The programmed cell death protein-1 (PD-1) signaling pathway inhibits immune effector responses against tumors, and immune checkpoint inhibitors that block this pathway are being increasingly used as cancer therapy. The objective of this study was to investigate whether this pathway contributes to persistent fungal infection and to determine whether anti-PD-1 Ab treatment improves fungal clearance...
October 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29038008/fibrinogen-cleavage-products-and-tlr4-promote-the-generation-of-programmed-cell-death-1-ligand-2-pd-l2-dendritic-cells-in-allergic-asthma
#18
Minkyoung Cho, Jeong-Eun Lee, Hoyong Lim, Hyun-Woo Shin, Roza Khalmuratova, Garam Choi, Hyuk Soon Kim, Wahn Soo Choi, Young-Jun Park, Inbo Shim, Byung-Seok Kim, Chang-Yuil Kang, Jae-Ouk Kim, Shinya Tanaka, Masato Kubo, Yeonseok Chung
BACKGROUND: Inhaled protease allergens preferentially trigger Th2-mediated inflammation in allergic asthma. The role of dendritic cells (DCs) on the induction of Th2 cell responses in allergic asthma has been well documented; however, the mechanism by which protease allergens induce Th2-favorable DCs in the airway remains unclear. OBJECTIVE: We sought to determine a subset of DCs responsible for Th2 cell responses in allergic asthma and the mechanism by which protease allergens induce the DC subset in the airway...
October 13, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29036261/development-of-halo-nevi-in-a-lung-cancer-patient-a-novel-immune-related-cutaneous-event-from-atezolizumab
#19
Mathew R Birnbaum, Michelle W Ma, Michael A Casey, Bijal D Amin, Mark Jacobson, Haiying Cheng, Beth N McLellan
Immunotherapy-induced vitiligo is an immune-related adverse event (irAE) observed in metastatic melanoma patients treated with immune checkpoint inhibitors that target the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1) pathways. To date, the development of leukoderma, poliosis, and halo nevi during immunotherapy has largely been reported in metastatic melanoma patients. We report a case of immunotherapy-induced leukoderma presenting as halo nevi in a patient with non-small cell lung cancer (NSCLC) treated with atezolizumab, a programmed cell death ligand (PD-L1) antibody...
October 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29035907/relationship-between-pd-l1-expression-and-cd8-t-cell-immune-responses-in-hepatocellular-carcinoma
#20
Chun-Yu Huang, Ying Wang, Guang-Yu Luo, Feng Han, Yong-Qiang Li, Zhong-Guo Zhou, Guo-Liang Xu
As PD-1/PD-L1 immune checkpoint inhibitors exhibited promising clinical outcomes in various types of solid tumors, PD-1/PD-L1 blockades have been explored for the treatment of hepatocellular carcinoma (HCC). However, the association of PD-L1 with antitumor immunoregulation is not clearly defined in HCC. Here, we evaluated the characteristics of PD-L1 expression, CD8 T-cell infiltration and their relationship in HCC. A total of 411 resected tumor specimens from HCC patients were immunostained for PD-L1 and CD8...
October 13, 2017: Journal of Immunotherapy
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