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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Pathogenesis of follicular lymphoma
TL;DR: Enhanced understanding of FL pathogenesis is currently leading to refined therapeutic targeting of perturbed biology, paving the way for precision medicine in this lymphoma subtype.
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Follicular lymphoma cell niche: identification of a preeminent IL-4-dependent T(FH)-B cell axis
Céline Pangault,Patricia Amé-Thomas,Philippe Ruminy,Delphine Rossille,Gersende Caron,Maryse Baia,J. De Vos,Mikael Roussel,Céline Monvoisin,Thierry Lamy,Hervé Tilly,P. Gaulard,Karin Tarte,Thierry Fest +13 more
TL;DR: It is demonstrated that tumor-infiltrating TFH specifically express functional IL-4 in FL, creating an IL- 4-dependent TFH–B cell axis that could sustain FL pathogenesis and represent a new potential therapeutic target.
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Increased angiogenic sprouting in poor prognosis FL is associated with elevated numbers of CD163+ macrophages within the immediate sprouting microenvironment
Andrew Clear,Abigail M. Lee,Maria Calaminici,Alan G. Ramsay,Kelly J. Morris,Simon Hallam,Gavin Kelly,Finlay MacDougall,T. Andrew Lister,John G. Gribben +9 more
TL;DR: Higher angiogenic activity in the poor prognostic group is revealed and an association between increased sprouting and elevated numbers of infiltrating CD163(+) macrophages within the immediate microenvironment surrounding the neovascular sprout is demonstrated.
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Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer.
Alberto Malesci,Paolo Bianchi,Giuseppe Celesti,Gianluca Basso,Federica Marchesi,Fabio Grizzi,Giuseppe Di Caro,Tommaso Cavalleri,Lorenza Rimassa,Richard Palmqvist,Alessandro Lugli,Viktor H. Koelzer,Massimo Roncalli,Alberto Mantovani,Shuji Ogino,Shuji Ogino,Luigi Laghi +16 more
TL;DR: High densities of TAMs, particularly in metastatic lymph-nodes, identify stage III colorectal cancer patients benefitting from 5-fluorouracil adjuvant therapy.
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Differential expression of NF-kappa B target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism
Rifat Hamoudi,A. Appert,Hongtao Ye,A. Ruskone-Fourmestraux,Berthold Streubel,Andreas Chott,Markus Raderer,Liping Gong,Iwona Wlodarska,C De Wolf-Peeters,K. A. MacLennan,L. de Leval,Peter G. Isaacson,M-Q Du +13 more
TL;DR: Gene set enrichment analysis (GSEA) of the NF-κB target genes and 4394 additional gene sets covering various cellular pathways, biological processes and molecular functions have shown that translocation-positive MALT lymphomas are characterized by an enhanced expression of NF-β target genes, particularly toll like receptor (TLR)6.
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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
TL;DR: The population of CD4+CD25+ immunoregulatory cells is characterized and it is demonstrated that they can suppress not only the induction of disease post-thymectomy, but can also efficiently suppress disease induced by cloned autoantigen-specific effector cells.
Journal ArticleDOI
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.
Journal ArticleDOI
Follicular Lymphoma International Prognostic Index.
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.
Follicular lymphoma international prognostic index.
Philippe Solal-Celigny,Pascal Roy,Philippe Colombat,J. M. White,James Olen Armitage,Reyes Arranz-Saez,Wing Yan Au,Monica Bellei,Pauline Brice,Dolores Caballero,Bertrand Coiffier,Eulogio Conde-Garcia,Chantal Doyen,Massimo Federico,Richard I. Fisher,Javier García-Conde,Cesare Guglielmi,Anton Hagenbeek,Corinne Haioun,Michael LeBlanc,Andrew Lister,Armando López-Guillermo,Peter McLaughlin,Noel Milpied,Pierre Morel,Nicolas Mounier,Stephen J. Proctor,Ama Z. S. Rohatiner,Paul Smith,Pierre Soubeyran,Hervé Tilly,Umberto Vitolo,Pier Luigi Zinzani,Emanuele Zucca,Emili Montserrat +34 more