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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The microenvironment in mature B-cell malignancies: a target for new treatment strategies
TL;DR: A paradigm shift in the treatment of selected B-cell malignancies is anticipated, moving from targeting primarily the malignant cells toward combining cytotoxic drugs with agents that interfere with the microenvironment's proactive role.
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The tumour microenvironment in B cell lymphomas
David W. Scott,Randy D. Gascoyne +1 more
TL;DR: A fundamental understanding of interactions between tumour cells and non-malignant cells gives insight into the pathogenesis of most B cell lymphomas and identifies novel therapeutic opportunities for targeting oncogenic pathways, both now and in the future.
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Systematic Analysis of Immune Infiltrates in High-Grade Serous Ovarian Cancer Reveals CD20, FoxP3 and TIA-1 as Positive Prognostic Factors
Katy Milne,Martin Köbel,Steven E. Kalloger,Rebecca O Barnes,Dongxia Gao,C. Blake Gilks,Peter H. Watson,Peter H. Watson,Peter H. Watson,Brad H. Nelson,Brad H. Nelson,Brad H. Nelson +11 more
TL;DR: Host immune responses to EOC vary widely according to histological subtype and the extent of residual disease, and TIA-1, FoxP3 and CD20 emerge as new positive prognostic factors in high-grade serous EOC from optimally debulked patients.
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Pathogenesis of follicular lymphoma
TL;DR: Crosstalk between neoplastic B cells and non-neoplastic immune and stromal cells in the microenvironment plays an important role in sustaining tumor cell growth, cultivating immune privilege, and promoting transformation.
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Follicular lymphoma cells induce T-cell immunologic synapse dysfunction that can be repaired with lenalidomide: implications for the tumor microenvironment and immunotherapy
Alan G. Ramsay,Andrew Clear,Gavin Kelly,Rewas Fatah,Janet Matthews,Finlay MacDougall,T. Andrew Lister,Abigail M. Lee,Maria Calaminici,John G. Gribben +9 more
TL;DR: In this article, the authors identify impaired T-cell immunologic synapse formation as an active immunosuppressive mechanism in follicular lymphoma (FL) and diffuse large B-cell lymphoma(DLBCL).
References
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Journal ArticleDOI
Immunohistochemical prognostic markers in diffuse large B-cell lymphoma: validation of tissue microarray as a prerequisite for broad clinical applications (a study from the Lunenburg Lymphoma Biomarker Consortium)
Daphne de Jong,Wanling Xie,Andreas Rosenwald,Mukesh Chhanabhai,Philippe Gaulard,Wolfram Klapper,Abigail M. Lee,Birgitta Sander,Christoph Thorns,Elias Campo,Thierry Jo Molina,Anton Hagenbeek,Sandra J. Horning,Andrew Lister,John M. M. Raemaekers,Gilles Salles,Randy D. Gascoyne,Edie Weller +17 more
TL;DR: Semi-quantitative immunohistochemistry for subclassification of DLBCL is feasible, but with varying rates of concordance for different markers and only using optimised techniques and strict scoring criteria is feasible.
Journal ArticleDOI
Molecular Pathogenesis of Follicular Lymphoma: A Cross Talk of Genetic and Immunologic Factors
TL;DR: Combined genetic and immunologic data may now support a model for the development of FL as a disease of functional B cells in which specific molecular alterations infer intrinsic growth properties of the tumor cells as well as dictate a specific functional cross talk with the immunologic regulatory network resulting in extrinsic growth support.
Journal ArticleDOI
CD8+ T-Cell Content in Diagnostic Lymph Nodes Measured by Flow Cytometry Is a Predictor of Survival in Follicular Lymphoma
TL;DR: Higher levels of CD8+ T cells predict a better prognosis, and these data support an important role for nonmalignant immune cells in the biology of follicular lymphoma.
Journal ArticleDOI
Follicular lymphoma: Have we made any progress?
TL;DR: The status of multiple options for treatment including interferon, fludarabine, dose intensification with autologous transplantation, therapy targeting the CD20 antigen and novel approaches is reviewed.
Journal ArticleDOI
Phase III Intergroup Study of Fludarabine Phosphate Compared With Cyclophosphamide, Vincristine, and Prednisone Chemotherapy in Newly Diagnosed Patients With Stage III and IV Low-Grade Malignant Non-Hodgkin's Lymphoma
Anton Hagenbeek,Houchingue Eghbali,Silvio Monfardini,Umberto Vitolo,Peter Hoskin,Christiane de Wolf-Peeters,Ken MacLennan,Elvira Staab-Renner,Joachim Kalmus,Astrid Schott,I. Teodorovic,Anastassia Negrouk,Martine Van Glabbeke,Robert Marcus +13 more
TL;DR: Overall response rates were significantly improved in the fludarabine arm versus the CVP arm, both for the intent-to-treat (ITT) population and assessable patients (P < .001).
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