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https://www.readbyqxmd.com/read/28783666/dynamics-of-influenza-induced-lung-resident-memory-t-cells-underlie-waning-heterosubtypic-immunity
#1
Bram Slütter, Natalija Van Braeckel-Budimir, Georges Abboud, Steven M Varga, Shahram Salek-Ardakani, John T Harty
Lung-resident memory CD8 T cells (TRM) induced by influenza A virus (IAV) that are pivotal for providing subtype-transcending protection against IAV infection (heterosubtypic immunity) are not maintained long term, causing gradual loss of protection. The short-lived nature of lung TRM contrasts sharply with long-term maintenance of TRM induced by localized infections in the skin and in other tissues. We show that the decline in lung TRM is determined by an imbalance between apoptosis and lung recruitment and conversion to TRM of circulating memory cells...
January 6, 2017: Science Immunology
https://www.readbyqxmd.com/read/28783656/resident-memory-cd8-t-cells-in-the-upper-respiratory-tract-prevent-pulmonary-influenza-virus-infection
#2
Angela Pizzolla, Thi H O Nguyen, Jeffrey M Smith, Andrew G Brooks, Katherine Kedzieska, William R Heath, Patrick C Reading, Linda M Wakim
Nasal epithelial tissue of the upper respiratory tract is the first site of contact by inhaled pathogens such as influenza virus. We show that this region is key to limiting viral spread to the lower respiratory tract and associated disease pathology. Immunization of the upper respiratory tract leads to the formation of local tissue-resident memory CD8(+) T cells (Trm cells). Unlike Trm cells in the lung, these cells develop independently of local cognate antigen recognition and transforming growth factor-β signaling and persist with minimal decay, representing a long-term protective population...
June 2, 2017: Science Immunology
https://www.readbyqxmd.com/read/28762602/hematopoietic-stem-cell-transplantation-in-pediatric-patients-with-acute-myeloid-leukemia-without-favorable-cytogenetics
#3
Jin Kyung Suh, Seong Wook Lee, Kyung-Nam Koh, Ho Joon Im, Eun Seok Choi, Seongsoo Jang, Chan-Jeoung Park, Jong Jin Seo
Intensified chemotherapy, HSCT, and supportive care improve the survival of pediatric patients with AML. However, no consensus has been reached regarding the role of HSCT in patients without favorable cytogenetics. We evaluated OS and EFS according to prognostic factors that affect clinical outcomes, including cytogenetics risk group, conditioning regimen, donor type, disease status at the time of HSCT, and number of chemotherapy cycles prior to HSCT in 65 pediatric patients with AML without favorable cytogenetics who underwent HSCT...
August 1, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28738020/resident-memory-t-cells-in-the-skin-mediate-durable-immunity-to-melanoma
#4
Brian T Malik, Katelyn T Byrne, Jennifer L Vella, Peisheng Zhang, Tamer B Shabaneh, Shannon M Steinberg, Aleksey K Molodtsov, Jacob S Bowers, Christina V Angeles, Chrystal M Paulos, Yina H Huang, Mary Jo Turk
Tissue-resident memory T (TRM) cells have been widely characterized in infectious disease settings; however, their role in mediating immunity to cancer remains unknown. We report that skin-resident memory T cell responses to melanoma are generated naturally as a result of autoimmune vitiligo. Melanoma antigen-specific TRM cells resided predominantly in melanocyte-depleted hair follicles and were maintained without recirculation or replenishment from the lymphoid compartment. These cells expressed CD103, CD69, and CLA (cutaneous lymphocyte antigen), but lacked PD-1 (programmed cell death protein-1) or LAG-3 (lymphocyte activation gene-3), and were capable of making IFN-γ (interferon-γ)...
April 14, 2017: Science Immunology
https://www.readbyqxmd.com/read/28733665/human-intrahepatic-cd69%C3%A2-%C3%A2-cd8-t-cells-have-a-tissue-resident-memory-t-cell-phenotype-with-reduced-cytolytic-capacity
#5
Femke Stelma, Annikki de Niet, Marjan J Sinnige, Karel A van Dort, Klaas P J M van Gisbergen, Joanne Verheij, Ester M M van Leeuwen, Neeltje A Kootstra, Hendrik W Reesink
Tissue resident memory T cells (TRM) have been identified in various tissues, however human liver TRM to date remain unidentified. TRM can be recognized by CD69 and/or CD103 expression and may play a role in the pathology of chronic hepatitis B (CHB) and hepatitis C virus infection (CHC). Liver and paired blood mononuclear cells from 17 patients (including 4 CHB and 6 CHC patients) were isolated and CD8+ T cells were comprehensively analysed by flowcytometry, immunohistochemistry and qPCR. The majority of intrahepatic CD8+ T cells expressed CD69, a marker used to identify TRM, of which a subset co-expressed CD103...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733265/outcomes-of-hematopoietic-stem-cell-transplantation-at-a-limited-resource-center-in-mexico-are-comparable-to-those-in-developed-countries
#6
Eucario Leon Rodriguez, Monica M Rivera Franco
The first hematopoietic stem cell transplantation (HSCT) in Mexico was performed at our institution in 1980. Eighteen years later, our HSCT program was restructured to reduce transplantation-related mortality (TRM) and improve overall survival (OS). The aim of this study was to describe outcomes of HSCT at our institution despite limited resources. Consecutive patients undergoing HSCT, from November 1998 to February 2017, were retrospectively analyzed at the National Institute of Medical Sciences and Nutrition Salvador Zubiran in Mexico City...
July 18, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28731654/validation-of-the-hematopoietic-cell-transplantation-specific-comorbidity-index-in-a-retrospective-cohort-of-children-and-adolescents-who-received-an-allogeneic-transplantation-in-argentina
#7
Carlos M Figueroa Turienzo, Carolina Cernadas, Mariana Roizen, Silvia Pizzi, Raquel Staciuk
INTRODUCTION: Hematopoietic cell transplantationis a therapy with a risk of transplant-related mortality (TRM), which may vary depending on prior comorbidities. The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) is an instrument developed to measure this risk. There are very few reports on its use in pediatrics. The objective of this study was to validate the HCT-CI in a pediatric cohort of allogeneic hematopoietic-cell transplantation recipients in Argentina. POPULATION AND METHODS: Retrospective cohort made up of 140 transplant patients at Hospital J...
August 1, 2017: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/28716387/respiratory-virus-prior-to-hematopoietic-cell-transplantation-is-associated-with-allo-immune-mediated-lung-syndromes
#8
Birgitta Versluys, Marc Bierings, Jean Luc Murk, Tom Wolfs, Caroline Lindemans, Kors Vd Ent, Jaap Jan Boelens
BACKGROUND: Allo-immune mediated lung syndromes (allo-LS) are life-threatening complications after hematopoietic cell transplantation (HCT). Respiratory virus (RV) has been suggested to play a role in the pathogenesis. OBJECTIVE: We studied the relation between RV-DNA/RNA detection in upper/lower airway before HCT and the occurrence of allo-LS. METHODS: We retrospectively analyzed all HCT recipients between 2004 and 2014, in whom Real-Time PCR for RV was done from Nasal-Pharyngeal-Aspirates (NPA) and Broncho-Alveolar- Lavage (BAL) before HCT...
July 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28714465/enhanced-anti-tumour-immunity-requires-the-interplay-between-resident-and-circulating-memory-cd8-t-cells
#9
Michel Enamorado, Salvador Iborra, Elena Priego, Francisco J Cueto, Juan A Quintana, Sarai Martínez-Cano, Ernesto Mejías-Pérez, Mariano Esteban, Ignacio Melero, Andrés Hidalgo, David Sancho
The goal of successful anti-tumoural immunity is the development of long-term protective immunity to prevent relapse. Infiltration of tumours with CD8(+) T cells with a resident memory (Trm) phenotype correlates with improved survival. However, the interplay of circulating CD8(+) T cells and Trm cells remains poorly explored in tumour immunity. Using different vaccination strategies that fine-tune the generation of Trm cells or circulating memory T cells, here we show that, while both subsets are sufficient for anti-tumour immunity, the presence of Trm cells improves anti-tumour efficacy...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28692028/in-search-of-the-optimal-platform-for-post-allogeneic-sct-immunotherapy-in-relapsed-multiple-myeloma-a-systematic-review
#10
REVIEW
R Oostvogels, S M U Venema, M de Witte, R Raymakers, J Kuball, N Kröger, M C Minnema
Allogeneic stem cell transplantation (allo-SCT) has the potential to induce sustained remissions in patients with multiple myeloma (MM). Currently, allo-SCT is primarily performed in high-risk MM patients, most often in the setting of early relapse after first-line therapy with autologous SCT. However, the implementation of allo-SCT for MM is jeopardized by high treatment-related mortality (TRM) rates as well as high relapse rates. In this systematic review, we aimed to identify a safe allo-SCT strategy that has optimal 1-year results regarding mortality, relapse and severe GvHD, creating opportunities for post-transplantation strategies to maintain remissions in the high-risk group of relapsed MM patients...
July 10, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28691152/reduced-bucy-2-and-g-csf-primed-bone-marrow-associates-with-low-graft-versus-host-disease-and-transplant-related-mortality-in-allogeneic-hsct
#11
Eucario Leon Rodriguez, Monica M Rivera Franco, Sandra I Perez Alvarez
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the ideal treatment for several diseases. However, the morbidity and mortality associated with the procedure might limit its widespread use; therefore, we implemented reduced BUCY2 as conditioning method along with the use of G-CSF-primed bone marrow (G-BM) in order to reduce complications, including graft-versus-host-disease (GVHD), and to improve survival in these patients. An analysis of transplant characteristics, complications, and survival of patients undergoing an allo-HSCT using this conditioning regimen (busulfan 12 mg/kg and cyclophosphamide 80 mg/kg) plus G-BM was performed...
September 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28684371/pharmacokinetics-and-model-based-dosing-to-optimize-fludarabine-therapy-in-pediatric-hematopoietic-cell-transplant-recipients
#12
Vijay Ivaturi, Christopher C Dvorak, Danna Chan, Tao Liu, Morton J Cowan, Justin Wahlstrom, Melisa Stricherz, Cathryn Jennissen, Paul J Orchard, Jakub Tolar, Sung-Yun Pai, Liusheng Huang, Francesca Aweeka, Janel Long-Boyle
A prospective multicenter study was conducted to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of fludarabine plasma (f-ara-a) and intracellular triphosphate (f-ara-ATP) in children undergoing hematopoietic cell transplantation (HCT) and receiving fludarabine with conditioning. Plasma and peripheral blood mononuclear cells (PBMCs) were collected over the course of therapy for quantitation of f-ara-a and f-ara-ATP. Nonlinear mixed-effects modeling was used to develop the PK model, including identification of covariates impacting drug disposition...
July 3, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28676100/superior-gvhd-free-relapse-free-survival-for-g-bm-to-g-pbsc-grafts-is-associated-with-higher-mdscs-content-in-allografting-for-patients-with-acute-leukemia
#13
Qian Fan, Hui Liu, Xinquan Liang, Ting Yang, Zhiping Fan, Fen Huang, Yiwen Ling, Xin Liao, Li Xuan, Na Xu, Xiaojun Xu, Jieyu Ye, Qifa Liu
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (G-PBSC) has largely replaced unstimulated bone marrow (un-BM) for allografting because of accelerated engraftment, but with a higher morbidity and mortality of graft-versus-host-disease (GVHD). Recent studies suggested that G-CSF-primed BM (G-BM) had similar engraftment but lower morbidity and mortality of GVHD comparing to G-PBSC. A prospective, randomized, multicenter study was conducted to compare G-BM with G-PBSC as the grafts in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia in first complete remission (CR1)...
July 4, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28675769/outcomes-of-allogeneic-stem-cell-transplantation-in-patients-with-paroxysmal-nocturnal-hemoglobinuria-with-or-without-aplastic-anemia
#14
Sung-Eun Lee, Sung Soo Park, Young-Woo Jeon, Jae-Ho Yoon, Byung-Sik Cho, Ki-Sung Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Hee-Je Kim, Seok-Goo Cho, Dong-Wook Kim, Woo-Sung Min, Jong Wook Lee
OBJECTIVE: The aim of this study was to evaluate the long-term outcomes of allogeneic stem cell transplantation (SCT) in patients with paroxysmal nocturnal hemoglobinuria (PNH) with or without aplastic anemia (AA). METHOD: A total of 33 patients with PNH clones who underwent allogeneic SCT were analyzed. RESULTS: After a median follow-up of 57 months (range, 6.0-151.3), the 5-year estimated overall survival rate was 87.9 ± 5.7%. Four patients died of transplant-related mortality (TRM)...
July 4, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28674027/increasing-use-of-allogeneic-hematopoietic-cell-transplantation-in-patients-age-70-years-and-older-in-the-united-states
#15
Lori Muffly, Marcelo C Pasquini, Michael Martens, Ruta Brazauskas, Xiaochun Zhu, Kehinde Adekola, Mahmoud Aljurf, Karen K Ballen, Ashish Bajel, Frederic Baron, Minoo Battiwalla, Amer Beitinjaneh, Jean-Yves Cahn, Mathew Carabasi, Yi-Bin Chen, Saurabh Chhabra, Stefan Ciurea, Edward Copelan, Anita D'Souza, John Edwards, James Foran, Cesar O Freytes, Henry C Fung, Robert Peter Gale, Sergio Giralt, Shahrukh K Hashmi, Gerhard C Hildebrandt, Vincent Ho, Ann Jakubowski, Hillard Lazarus, Marlise R Luskin, Rodrigo Martino, Richard Maziarz, Philip McCarthy, Taiga Nishihori, Rebecca Olin, Richard F Olsson, Attaphol Pawarode, Edward Peres, Andrew R Rezvani, David Rizzieri, Bipin N Savani, Harry C Schouten, Mitchell Sabloff, Matthew Seftel, Sachiko Seo, Mohamed L Sorror, Jeff Szer, Baldeep M Wirk, William A Wood, Andrew Artz
PURPOSE: To evaluate trends and outcomes of allogeneic HCT in adults ≥70 years with hematologic malignancies across the United States (US). PATIENTS AND METHODS: Adults 70 years and older with a hematologic malignancy undergoing first allogeneic HCT in the US between 2000 and 2013 and reported to the CIBMTR were eligible. Transplant utilization and transplant outcomes including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied...
July 3, 2017: Blood
https://www.readbyqxmd.com/read/28659478/enfuvirtide-t20-based-lipopeptide-is-a-potent-hiv-1-cell-fusion-inhibitor-implication-for-viral-entry-and-inhibition
#16
Xiaohui Ding, Xiujuan Zhang, Huihui Chong, Yuanmei Zhu, Huamian Wei, Xiyuan Wu, Jinsheng He, Xinquan Wang, Yuxian He
The peptide drug Enfuvirtide (T20) is the only viral fusion inhibitor used in combination therapy of HIV-1 infection, but it has a relatively low antiviral activity and easily induces drug-resistance. Emerging studies demonstrate that lipopeptide-based fusion inhibitors have greatly improved antiviral potency and in vivo stability, such as LP-11 and LP-19 that mainly target the gp41 pocket site. In this study, we focused on developing a T20-based lipopeptide inhibitor that lacks pocket-binding sequence and targets a different site...
June 28, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28650455/clinical-impact-of-nk-cell-reconstitution-after-reduced-intensity-conditioned-unrelated-cord-blood-transplantation-in-patients-with-acute-myeloid-leukemia-analysis-of-a-prospective-phase-ii-multicenter-trial-on-behalf-of-the-soci%C3%A3-t%C3%A3-fran%C3%A3-aise-de-greffe-de
#17
S Nguyen, A Achour, L Souchet, S Vigouroux, P Chevallier, S Furst, A Sirvent, J-O Bay, G Socié, P Ceballos, A Huynh, J Cornillon, S Francois, F Legrand, I Yakoub-Agha, G Michel, N Maillard, G Margueritte, S Maury, M Uzunov, C-E Bulabois, M Michallet, L Clement, C Dauriac, K Bilger, J Lejeune, V Béziat, V Rocha, B Rio, S Chevret, V Vieillard
Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial...
June 26, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28628092/tissue-resident-memory-features-are-linked-to-the-magnitude-of-cytotoxic-t-cell-responses-in-human-lung-cancer
#18
Anusha-Preethi Ganesan, James Clarke, Oliver Wood, Eva M Garrido-Martin, Serena J Chee, Toby Mellows, Daniela Samaniego-Castruita, Divya Singh, Grégory Seumois, Aiman Alzetani, Edwin Woo, Peter S Friedmann, Emma V King, Gareth J Thomas, Tilman Sanchez-Elsner, Pandurangan Vijayanand, Christian H Ottensmeier
Therapies that boost the anti-tumor responses of cytotoxic T lymphocytes (CTLs) have shown promise; however, clinical responses to the immunotherapeutic agents currently available vary considerably, and the molecular basis of this is unclear. We performed transcriptomic profiling of tumor-infiltrating CTLs from treatment-naive patients with lung cancer to define the molecular features associated with the robustness of anti-tumor immune responses. We observed considerable heterogeneity in the expression of molecules associated with activation of the T cell antigen receptor (TCR) and of immunological-checkpoint molecules such as 4-1BB, PD-1 and TIM-3...
August 2017: Nature Immunology
https://www.readbyqxmd.com/read/28620836/sox2-immunity-and-tissue-resident-memory-in-children-and-young-adults-with-glioma
#19
Juan C Vasquez, Anita Huttner, Lin Zhang, Asher Marks, Amy Chan, Joachim M Baehring, Kristopher T Kahle, Kavita M Dhodapkar
Therapies targeting immune checkpoints are effective in tumors with a high mutation burden that express multiple neo-antigens. However, glial tumors including those seen in children carry fewer mutations and there is an unmet need to identify new antigenic targets of anti-tumor immunity. SOX2 is an embryonal stem cell antigen implicated in the biology of glioma initiating cells. Expression of SOX2 by pediatric glial tumors and the capacity of the immune system in these patients to recognize SOX2 has not been previously studied...
August 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28581467/directionality-of-non-permissive-hla-dpb1-t-cell-epitope-group-mismatches-does-not-improve-clinical-risk-stratification-in-8-8-matched-unrelated-donor-hematopoietic-cell-transplantation
#20
K Fleischhauer, K W Ahn, H L Wang, L Zito, P Crivello, C Müller, M Verneris, B E Shaw, J Pidala, M Oudshorn, S J Lee, S R Spellman
In 8/8 HLA-matched unrelated donor (UD) hematopoietic cell transplants (HCT), HLA-DPB1 mismatches between alleles from different T-cell epitope (TCE) groups (non-permissive mismatches) are associated with significantly higher risks of mortality compared with those between alleles from the same TCE group (permissive mismatches); however, the relevance of mismatch directionality, that is (host vs graft (uni-directional HvG), graft vs host (uni-directional GvH) or both (bi-directional) in the non-permissive setting is unknown...
June 5, 2017: Bone Marrow Transplantation
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