Impact of the tumor microenvironment on prognosis in follicular lymphoma is dependent on specific treatment protocols
Daphne de Jong,Ad Koster,Anton Hagenbeek,John M. M. Raemaekers,Dennis Veldhuizen,Sabien Heisterkamp,Jan de Boer,Martine Van Glabbeke +7 more
TLDR
It is suggestive that a dense infiltrate of FoxP3-positive T cells, dense and interfollicular infiltrate of CD68-positive macrophages and complete follicular dendritic meshworks were associated with a favorable time to progression in CVP-treated patients, while being poor prognostic sign in fludarabine- treated patients.Abstract:
Background The clinical behavior of follicular lymphoma is largely determined by properties of the non-malignant tumor microenvironment. The precise nature of the cell populations is still unclear and published data on their prognostic significance are highly conflicting. This may be partly due to heterogeneous composition and tr eatments. Design and Methods Pre-treatment biopsy samples of patients with follicular lymphoma treated in an EORTC/BNLI trial comparing fludarabine to cyclophosphamide, vincristine and prednisone (CVP) chemotherapy could be retrieved for 61 patients in five Eur opean countries. Immunohistochemical investigations were performed to evaluate tumor cell characteristics, T-cell subsets, follicular dendritic cells and macrophages and associations with clinical outcome were studied. Results Some markers showed a homogeneous prognostic impact, while others had a different and sometimes opposite effect in the treatment arms. CD69 expression on tumor cells was a poor prognostic sign and an interfollicular infiltrate of FoxP3-positive T cells was a good prognostic sign irrespective of the treatment arm. It is suggestive that a dense infiltrate of FoxP3-positive T cells, a dense and interfollicular infiltrate of CD68-positive macr ophages and complete follicular dendritic meshworks were associated with a favorable time to progression in CVP-treated patients, while being a poor prognostic sign in fludarabine-treated patients. Conclusions Our results suggest that characteristic properties of the microenvironment in follicular lymphoma determines the responses to essentially different chemotherapeutic approaches. These data may provide an explanation for the highly conflicting r esults on immunohistochemical markers and the prognostic role of the microenvironment in follicular lymphoma reported thus far and lay the basis for the development of predictive assays to tailor treatment in patients with follicular lymphoma.read more
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Improved demonstration of immunohistochemical prognostic markers for survival in follicular lymphoma cells
Francisca I. Camacho,Carmen Bellas,Cesareo Corbacho,Alexia Caleo,Reyes Arranz-Saez,Jimena Cannata,Javier Menárguez,Lydia Sanchez-Verde,Leocricia González-Camacho,Ma Elena Pérez-Martín,Miguel Ángel Martínez-González,Tomás Álvaro,Manuela Mollejo,Carmen Ruiz-Marcellan,Carlos Montalbán,Miguel A. Piris +15 more
TL;DR: A potentially useful finding is that the integrated FLIPI plus immunohistochemical model can be used to identify a subset of 26 patients, with a survival probability of 100% at 5 years, which indicates that a group of FL cases may have a very good clinical course, and indicates that this group can be identified using this integrated clinical and immunohISTochemical approach.
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Gene expression profiling in follicular lymphoma and its implication for clinical practice.
Andrea Janíková,Boris Tichy,Jana Šupíková,Katerina Stano-Kozubik,Šárka Pospíšilová,Leos Kren,Ingrid Vášová,David Šálek,Jiri Mayer +8 more
TL;DR: The hypothesis that the number of T-cells and their expression pattern play a major role in FL development is supported.
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Context-explorer: Analysis of spatially organized protein expression in high-throughput screens.
TL;DR: Context-explorer (CE), a software tool to improve investigation cell fate acquisitions through community level analyses, is demonstrated in the analysis of human and mouse pluripotent stem cells patterned in colonies of defined geometries in multi-well plates.
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Assessing the prognostic impact of immune cell infiltrates in follicular lymphoma.
TL;DR: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma subtype in the Western world and over time a significant proportion of patients progress to aggressive, often therapy-refractory and ultimately fatal disease.
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Low rate of spleen involvement in sporadic Burkitt lymphoma at staging on PET-CT
Tima Davidson,Tima Davidson,Eldar Priel,Ginette Schiby,Ginette Schiby,Stephen Raskin,Bar Chikman,Ella Nissan,Ohad Benjamini,Ohad Benjamini,Johnatan Nissan,Elinor Goshen,Elinor Goshen,Simona Ben-Haim,Simona Ben-Haim,Ophira Salomon,Ophira Salomon,Abraham Avigdor,Abraham Avigdor +18 more
TL;DR: The spleen is rarely involved in SBL at the time of staging, according to PET-CT, except in cases with direct extension from adjacent peritoneal mass, and the low rate of spleen involvement may serve as a specific characteristic of SBL.
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TL;DR: The Follicular Lymphoma International Prognostic Index was designed from the data recorded over 8 years of nearly 5000 patients registered worldwide to help provide an optimal treatment option for patients with follicular lymphoma.
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Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells
Sandeep S. Dave,George E. Wright,Bruce K. Tan,Andreas Rosenwald,Andreas Rosenwald,Randy D. Gascoyne,Wing C. Chan,Richard I. Fisher,Rita M. Braziel,Lisa M. Rimsza,Thomas M. Grogan,Thomas P. Miller,Michael LeBlanc,Timothy C. Greiner,Dennis D. Weisenburger,James C. Lynch,Julie M. Vose,James O. Armitage,Erlend B. Smeland,Stein Kvaløy,Harald Holte,Jan Delabie,Joseph M. Connors,Peter M. Lansdorp,Qin Ouyang,T. Andrew Lister,Andrew Davies,Andrew J. Norton,H. Konrad Muller-Hermelink,German Ott,Elias Campo,Emilio Montserrat,Wyndham H. Wilson,Elaine S. Jaffe,Richard M. Simon,Liming Yang,John Powell,Hong Zhao,Neta Goldschmidt,Michael Chiorazzi,Louis M. Staudt +40 more
TL;DR: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.
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CD4+CD25+ T Cells Inhibit Both the Induction and Effector Function of Autoreactive T Cells and Represent a Unique Lineage of Immunoregulatory Cells
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Inhibition of CD4+25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide
M. E. Christine Lutsiak,Roshanak Tolouei Semnani,Roberto De Pascalis,Syed V. S. Kashmiri,Jeffrey Schlom,Helen Sabzevari +5 more
TL;DR: This is the first report demonstrating that CY, in addition to decreasing cell number, inhibits the suppressive capability of T(REGs), and the relevance of the loss of suppressor functionality and the changes in gene expression are discussed.
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TL;DR: The Follicular Lymphoma International Prognostic Index was designed from the data recorded over 8 years of nearly 5000 patients registered worldwide to help provide an optimal treatment option for patients with follicular lymphoma.
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High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma.
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