Impact of the tumor microenvironment on prognosis in follicular lymphoma is dependent on specific treatment protocols
TL;DR: 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.
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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.
543 citations
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.
Abstract: B cell lymphomas are cancers that arise from cells that depend on numerous highly orchestrated interactions with immune and stromal cells in the course of normal development. Despite the recent focus on dissecting the genetic aberrations within cancer cells, it has been increasingly recognized that tumour cells retain a range of dependence on interactions with the non-malignant cells and stromal elements that constitute the tumour microenvironment. A fundamental understanding of these interactions gives insight into the pathogenesis of most B cell lymphomas and, moreover, identifies novel therapeutic opportunities for targeting oncogenic pathways, both now and in the future.
392 citations
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.
Abstract: Background
Tumor-infiltrating T cells are associated with survival in epithelial ovarian cancer (EOC), but their functional status is poorly understood, especially relative to the different risk categories and histological subtypes of EOC.
368 citations
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.
Abstract: The hallmark t(14;18)(q32;q21) in follicular lymphoma (FL) results in constitutive overexpression of the BCL2 protein, allowing B cells to abrogate the default germinal center apoptotic program. Most tumors are characterized by recurrent secondary genetic alterations including genomic gains, losses, and mutations, some providing a growth advantage, including alterations in MLL2, EPHA7, TNFRSF14, and EZH2. The sequence in which these events occur and how they contribute to progression and ultimately to transformation is unclear. Lastly, 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.
257 citations
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).
225 citations
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TL;DR: This report contains the proceedings of the Second International Lunenburg LymphomaWorkshop, held at the Lunenburg Estate in Langbroek, the Netherlands on May 19 and 20, 2003, and aimed at integrating current clinical knowledge with novel biological insights to improve on the prognostic stratification of patients with FL and DLCL.
Abstract: This report contains the proceedings of the Second International Lunenburg LymphomaWorkshop, held at the Lunenburg Estate in Langbroek, the Netherlands on May 19 and 20, 2003. In this workshop 26 international lymphoma experts from the fields of hematology and pathology were assembled to discuss old and new prognostic factors in follicular non-Hodgkin’s lymphoma (FL) and diffuse large-cell lymphoma (DLCL). The ultimate goal of the meeting was to start integrating current clinical knowledge with novel biological insights to improve on the prognostic stratification of patients with FL and DLCL. The meeting was sponsored by the Ank van Vlissingen Foundation, a private foundation established in 1980 that aims at promoting lymphoma research and treatment. The First Lunenburg Lymphoma Workshop was held in May 2001, and focussed on ongoing clinical trials.
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