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https://www.readbyqxmd.com/read/29416939/maturation-of-tertiary-lymphoid-structures-and-recurrence-of-stage-ii-and-iii-colorectal-cancer
#1
Florian Posch, Karina Silina, Sebastian Leibl, Axel Mündlein, Holger Moch, Alexander Siebenhüner, Panagiotis Samaras, Jakob Riedl, Michael Stotz, Joanna Szkandera, Herbert Stöger, Martin Pichler, Roger Stupp, Maries van den Broek, Peter Schraml, Armin Gerger, Ulf Petrausch, Thomas Winder
Tertiary lymphoid structures (TLS) are associated with favorable outcome in non-metastatic colorectal carcinoma (nmCRC), but the dynamics of TLS maturation and its association with effective anti-tumor immune surveillance in nmCRC are unclear. Here, we hypothesized that not only the number of TLS but also their composition harbors information on recurrence risk in nmCRC. In a comprehensive molecular, tissue, laboratory, and clinical analysis of 109 patients with stage II/III nmCRC, we assessed TLS numbers and degree of maturation in surgical specimens by multi-parameter immunofluorescence of follicular dendritic cell (FDC) and germinal center (GC) markers...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29279354/germinal-centers-determine-the-prognostic-relevance-of-tertiary-lymphoid-structures-and-are-impaired-by-corticosteroids-in-lung-squamous-cell-carcinoma
#2
Karina Silina, Alex Soltermann, Farkhondeh Movahedian Attar, Ruben Casanova, Zina M Uckeley, Helen Thut, Muriel Wandres, Sergejs Isajevs, Phil F Cheng, Alessandra Curioni Fontecedro, Periklis Foukas, Mitchell P Levesque, Holger Moch, Aija Linē, Maries van den Broek
In solid tumors, the presence of lymph node-like structures called tertiary lymphoid structures (TLS) is associated with improved patient survival. However, little is known about how TLS form in cancer, how their function affects survival, and whether they are affected by cancer therapy. In this study, we used multi-spectral microscopy, quantitative pathology and gene expression profiling to analyze TLS formation in human lung squamous cell carcinoma (LSCC) and in an experimental model of lung TLS induction...
December 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/29218052/spoiling-for-a-fight-b-lymphocytes-as-initiator-and-effector-populations-within-tertiary-lymphoid-organs-in-autoimmunity-and-transplantation
#3
REVIEW
Jawaher Alsughayyir, Gavin J Pettigrew, Reza Motallebzadeh
Tertiary lymphoid organs (TLOs) develop at ectopic sites within chronically inflamed tissues, such as in autoimmunity and rejecting organ allografts. TLOs differ structurally from canonical secondary lymphoid organs (SLOs), in that they lack a mantle zone and are not encapsulated, suggesting that they may provide unique immune function. A notable feature of TLOs is the frequent presence of structures typical of germinal centers (GCs). However, little is known about the role of such GCs, and in particular, it is not clear if the B cell response within is autonomous, or whether it synergizes with concurrent responses in SLOs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29152550/tertiary-lymphoid-structures-associate-with-tumour-stage-in-urothelial-bladder-cancer
#4
Madhuri Koti, Amanda Shou Xu, Kevin Yi Mi Ren, Kash Visram, Runhan Ren, David M Berman, D Robert Siemens
Background: Urothelial bladder cancer (UBC) is a highly prevalent disease in North America, however its optimal management remains elusive. The contribution of B cell associated responses is poorly understood in bladder cancer. Lymphoid neogenesis is a hallmark of an active immune response at tumor sites that sometimes leads to formation of tertiary lymphoid structures (TLS) that resemble germinal centers formed in secondary lymphoid organs. Objective: This study was conducted with an aim to investigate the presence and characteristics of TLS in UBC with a focus to compare and contrast the TLS formation in treatment naive low grade non-muscle invasive (NMIBC) and muscle invasive bladder cancers (MIBC)...
October 27, 2017: Bladder Cancer
https://www.readbyqxmd.com/read/29125185/thymus-involvement-in-early-onset-myasthenia-gravis
#5
REVIEW
Mélanie A Cron, Solène Maillard, José Villegas, Frédérique Truffault, Muriel Sudres, Nadine Dragin, Sonia Berrih-Aknin, Rozen Le Panse
It has long been established that the thymus plays a central role in autoimmune myasthenia gravis (MG) because of either thymoma or thymic hyperplasia of lymphoproliferative origin. In this review, we discuss thymic changes associated with thymic hyperplasia and their implications in the development of an autoimmune response against the acetylcholine receptor (AChR).The hyperplastic MG thymus displays all the characteristics of tertiary lymphoid organs (TLOs): neoangiogenic processes with high endothelial venule and lymphatic vessel development, chemokine overexpression favoring peripheral cell recruitment, and ectopic germinal center development...
January 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28970832/use-of-toll-like-receptor-agonists-to-induce-ectopic-lymphoid-structures-in-myasthenia-gravis-mouse-models
#6
Marieke Robinet, Bérengère Villeret, Solène Maillard, Mélanie A Cron, Sonia Berrih-Aknin, Rozen Le Panse
Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction. MG symptoms are characterized by muscle weaknesses. The thymus of MG patients is very often abnormal and possesses all the characteristics of tertiary lymphoid organs such as neoangiogenesis processes, overexpression of inflammatory cytokines and chemokines, and infiltration of B lymphocytes leading to ectopic germinal center (GC) development. We previously demonstrated that injections of mice with polyinosinic-polycytidylic acid [Poly(I:C)], a synthetic double-stranded RNA mimicking viral infection, induce thymic changes and trigger MG symptoms...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28730224/histopathological-and-immunohistochemical-profile-in-primary-sj%C3%A3-gren-s-syndrome
#7
Ştefan Cristian Dinescu, Mircea Cătălin ForŢofoiu, Ana Maria Bumbea, Paulina Lucia Ciurea, Cristina Jana Busuioc, Anca Emanuela Muşetescu
Sjögren's syndrome (SS) is an autoimmune disease characterized by hypofunction of the salivary and lachrymal glands. Main clinical features of SS are sicca symptoms, due to the altered glandular function. Also, in advanced stages, bilateral swelling of the parotid glands can be noted, indicative of severe glandular involvement. Phenotypic expression of various mononuclear cells present in the affected tissue offers additional insight into cellular proliferation, survival, migration, antibody secretion and also the potential of forming tertiary lymphoid tissue, i...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28688665/b-cells-in-tertiary-lymphoid-structures-are-associated-with-favorable-prognosis-in-gastric-cancer
#8
Chie Sakimura, Hiroaki Tanaka, Takahiro Okuno, Soichiro Hiramatsu, Kazuya Muguruma, Kosei Hirakawa, Hideki Wanibuchi, Masaichi Ohira
BACKGROUND: The role of tumor-infiltrating B cells in the tumor microenvironment is still unclear. Recent studies have reported that B cells and tertiary lymphoid structures (TLSs) that contain B cell follicles correlate with the favorable prognosis of cancer patients. The aim of this study was to investigate the association between tumor-infiltrating B cells and clinicopathological features in gastric cancer. METHODS: Tumor blocks were obtained from 226 patients with stage Ib to stage IV gastric cancer...
July 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28680760/tbet-and-il-36%C3%AE-cooperate-in-therapeutic-dc-mediated-promotion-of-ectopic-lymphoid-organogenesis-in-the-tumor-microenvironment
#9
Aliyah M Weinstein, Lu Chen, Emily A Brzana, Prashanti R Patil, Jennifer L Taylor, Kellsye L Fabian, Callen T Wallace, Sabrina D Jones, Simon C Watkins, Binfeng Lu, David F Stroncek, Timothy L Denning, Yang-Xin Fu, Peter A Cohen, Walter J Storkus
We have previously reported that direct injection of dendritic cells (DC) engineered to express the Type-1 transactivator Tbet (i.e., DC.Tbet) into murine tumors results in antitumor efficacy in association with the development of structures resembling tertiary lymphoid organs (TLO) in the tumor microenvironment (TME). These TLO contained robust infiltrates of B cells, DC, NK cells, and T cells in proximity to PNAd(+) blood vessels; however, they were considered incomplete, since the recruited B cells failed to organize into classic germinal center-like structures...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28589352/isolation-and-characterization-of-mouse-and-human-follicular-dendritic-cells
#10
Mohey Eldin M El Shikh, Riham El Sayed, Costantino Pitzalis
Follicular dendritic cells (FDCs) reside in the B cell follicles of secondary and tertiary lymphoid tissues where they play key roles in the development and maintenance of lymphoid tissue architecture and function. FDCs trap native antigens for extended periods of time in the form of immune complexes which critcally regulate germinal center reactions in health and disease. Here, we describe how to isolate and characterize FDCs from murine and human lymphoid tissues.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28570278/cxcl13-producing-tfh-cells-link-immune-suppression-and-adaptive-memory-in-human-breast-cancer
#11
Chunyan Gu-Trantien, Edoardo Migliori, Laurence Buisseret, Alexandre de Wind, Sylvain Brohée, Soizic Garaud, Grégory Noël, Vu Luan Dang Chi, Jean-Nicolas Lodewyckx, Céline Naveaux, Hugues Duvillier, Stanislas Goriely, Denis Larsimont, Karen Willard-Gallo
T follicular helper cells (TFH cells) are important regulators of antigen-specific B cell responses. The B cell chemoattractant CXCL13 has recently been linked with TFH cell infiltration and improved survival in human cancer. Although human TFH cells can produce CXCL13, their immune functions are currently unknown. This study presents data from human breast cancer, advocating a role for tumor-infiltrating CXCL13-producing (CXCR5-) TFH cells, here named TFHX13 cells, in promoting local memory B cell differentiation...
June 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/27799933/ectopic-lymphoid-structures-powerhouse-of-autoimmunity
#12
REVIEW
Elisa Corsiero, Alessandra Nerviani, Michele Bombardieri, Costantino Pitzalis
Ectopic lymphoid structures (ELS) often develop at sites of inflammation in target tissues of autoimmune diseases, such as rheumatoid arthritis, Sjögren's syndrome, multiple sclerosis, myasthenia gravis, and systemic lupus erythematosus. ELS are characterized by the formation of organized T/B cells aggregates, which can acquire follicular dendritic cells network supporting an ectopic germinal center response. In this review, we shall summarize the mechanisms that regulate the formation of ELS in tertiary lymphoid organs, with particular emphasis on the role of lymphoid chemokines in both formation and maintenance of ELS, the role of emerging positive and negative regulators of ELS development and function, including T follicular helper cells and IL-27, respectively...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27799872/potential-of-cells-and-cytokines-chemokines-to-regulate-tertiary-lymphoid-structures-in-human-diseases
#13
REVIEW
Feifeng Jing, Eun Young Choi
Tertiary lymphoid structures (TLS) are ectopic lymphoid tissues involved in chronic inflammation, autoimmune diseases, transplant rejection and cancer. They exhibit almost all the characteristics of secondary lymphoid organs (SLO), which are associated with adaptive immune responses; as such, they contain organized B-cell follicles with germinal centers, distinct areas containing T cells and dendritic cells, high endothelial venules, and lymphatics. In this review, we briefly describe the formation of SLO, and describe the cellular subsets and molecular cues involved in the formation and maintenance of TLS...
October 2016: Immune Network
https://www.readbyqxmd.com/read/27798262/autoimmune-manifestations-in-aged-mice-arise-from-early-life-immune-dysregulation
#14
Tamer I Mahmoud, Jingya Wang, Jodi L Karnell, Qiming Wang, Shu Wang, Brian Naiman, Phillip Gross, Philip Z Brohawn, Chris Morehouse, Jordan Aoyama, Clive Wasserfall, Laura Carter, Mark A Atkinson, David V Serreze, Helen Braley-Mullen, Tomas Mustelin, Roland Kolbeck, Ronald Herbst, Rachel Ettinger
Autoantibodies can be present years to decades before the onset of disease manifestations in autoimmunity. This finding suggests that the initial autoimmune trigger involves a peripheral lymphoid component, which ultimately drives disease pathology in local tissues later in life. We show that Sjögren's syndrome manifestations that develop in aged NOD.H-2h4 mice were driven by and dependent on peripheral dysregulation that arose in early life. Specifically, elimination of spontaneous germinal centers in spleens of young NOD...
October 19, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27752256/understanding-immune-cells-in-tertiary-lymphoid-organ-development-it-is-all-starting-to-come-together
#15
REVIEW
Gareth W Jones, David G Hill, Simon A Jones
Tertiary lymphoid organs (TLOs) are frequently observed in tissues affected by non-resolving inflammation as a result of infection, autoimmunity, cancer, and allograft rejection. These highly ordered structures resemble the cellular composition of lymphoid follicles typically associated with the spleen and lymph node compartments. Although TLOs within tissues show varying degrees of organization, they frequently display evidence of segregated T and B cell zones, follicular dendritic cell networks, a supporting stromal reticulum, and high endothelial venules...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27688606/hiv-associated-hematologic-malignancies-experience-from-a-tertiary-cancer-center-in-india
#16
Rakesh Reddy, Ajay Gogia, Lalit Kumar, Atul Sharma, Sameer Bakhshi, Mehar C Sharma, Saumyaranjan Mallick, Ranjit Sahoo
CONTEXT AND AIM: Data on HIV associated hematologic malignancies is sparse from India. This study attempts to analyze the spectrum and features of this disease at a tertiary cancer center in India. SETTING AND METHODS: Retrospective study from case records of patients registered with a diagnosis of hematologic malignancy and HIV infection between January 2010 and June 2015. RESULTS: Thirteen cases of HIV associated hematologic malignancies were identified, six of them pediatric...
July 2016: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/27579026/early-il-1-signaling-promotes-ibalt-induction-after-influenza-virus-infection
#17
Katrijn Neyt, Corine H GeurtsvanKessel, Kim Deswarte, Hamida Hammad, Bart N Lambrecht
Inducible bronchus-associated lymphoid tissue (iBALT) is a long lasting tertiary lymphoid tissue that can be induced following influenza A virus (IAV) infection. Previous studies have shown that iBALT structures containing germinal center (GC) B cells protect against repeated infection by contributing locally to the cellular and humoral immune response. If we are to exploit this in vaccination strategies, we need a better understanding on how iBALT structures are induced. One hypothesis is that the strength of the initial innate response dictates induction of iBALT...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27446069/how-follicular-dendritic-cells-shape-the-b-cell-antigenome
#18
REVIEW
Jan Kranich, Nike Julia Krautler
Follicular dendritic cells (FDCs) are stromal cells residing in primary follicles and in germinal centers of secondary and tertiary lymphoid organs (SLOs and TLOs). There, they play a crucial role in B-cell activation and affinity maturation of antibodies. FDCs have the unique capacity to bind and retain native antigen in B-cell follicles for long periods of time. Therefore, FDCs shape the B-cell antigenome (the sum of all B-cell antigens) in SLOs and TLOs. In this review, we discuss recent findings that explain how this stromal cell type can arise in almost any tissue during TLO formation and, furthermore, focus on the mechanisms of antigen capture and retention involved in the generation of long-lasting antigen depots displayed on FDCs...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27148274/tertiary-lymphoid-organs-in-takayasu-arteritis
#19
Marc Clement, Adrien Galy, Patrick Bruneval, Marion Morvan, Fabien Hyafil, Khadija Benali, Nicoletta Pasi, Lydia Deschamps, Quentin Pellenc, Thomas Papo, Antonino Nicoletti, Karim Sacre
OBJECTIVE: The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients. METHODS: Hematoxylin and eosin-stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27141376/spatial-distribution-of-b-cells-predicts-prognosis-in-human-pancreatic-adenocarcinoma
#20
Giovanni Francesco Castino, Nina Cortese, Giovanni Capretti, Simone Serio, Giuseppe Di Caro, Rossana Mineri, Elena Magrini, Fabio Grizzi, Paola Cappello, Francesco Novelli, Paola Spaggiari, Massimo Roncalli, Cristina Ridolfi, Francesca Gavazzi, Alessandro Zerbi, Paola Allavena, Federica Marchesi
B-cell responses are emerging as critical regulators of cancer progression. In this study, we investigated the role of B lymphocytes in the microenvironment of human pancreatic ductal adenocarcinoma (PDAC), in a retrospective consecutive series of 104 PDAC patients and in PDAC preclinical models. Immunohistochemical analysis revealed that B cells occupy two histologically distinct compartments in human PDAC, either scatteringly infiltrating (CD20-TILs), or organized in tertiary lymphoid tissue (CD20-TLT). Only when retained within TLT, high density of B cells predicted longer survival (median survival 16...
April 2016: Oncoimmunology
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