Good prognosis for follicular lymphoma with estrogen receptor α‐positive follicular dendritic cells

Ohe, Rintaro; Meng, Hongxue; Yamada, Akane; Aung, Naing Ye; Kabasawa, Takanobu; Tamura, Yuka; Utsunomiya, Aya; Tamazawa, Nobuyuki; Kawamura, Ichiro; Kitaoka, Takumi; Suzuki, Kazushi; Yanagiya, Ryo; Toubai, Tomomi; Ishizawa, Kenichi; Yamakawa, Mitsunori

doi:10.1002/hon.2730

Cited by 4 publications

(2 citation statements)

References 28 publications

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“…In FL, FDC phenotype recapitulates that observed in GC dark zone FDC, with positivity for CD21 and Clusterin, but weak or negative expression of CD23, CD35 and ICAM1 5 , 27 , 32 . Recently, the expression of estrogen receptor in FDC in cases FL was found to be associated with low grade and good prognosis 41 , while positivity of CD14 was an independent predictor of transformation into large B cell lymphoma 29 .…”

Section: Fdc In Hematological Disordersmentioning

confidence: 99%

Follicular dendritic cell sarcoma

2021

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Summary Follicular dendritic cells (FDC) are mesenchymal-derived dendritic cells located in B-follicles where they play a pivotal role in triggering and maintaining B-cell adaptive immune response. In 1986 Dr. Juan Rosai first reported a series of neoplasms showing features of FDC and defined it as Follicular Dendritic Cell Tumor, subsequently renamed as “sarcoma” (FDCS). In its seminal and subsequent articles Rosai and colleagues highlighted the heterogeneous microscopic appearance of FDCS and its immunohistochemical and ultrastructural features. FDCS mostly occurs in extranodal sites (79.4% of cases) and lymph nodes (15.1%); in about 7%-10% of cases it is associated with hyaline-vascular Castleman disease. Given its significant growth pattern and cytological variability, FDCS can be confused with various neoplasms and even inflammatory processes. The diagnosis requires the use of a broad spectrum of FDC markers (e.g. CD21, CD23, CD35, clusterin, CXCL13, podoplanin), particularly considering that tumor antigen-loss is frequent. The inflammatory-pseudotumor-like (IPT-like) variant of FDCS, in addition to its peculiar histopathological and clinical features, is characterized by positivity of tumor cells for Epstein-Barr virus, representing a diagnostic requisite. No distinctive genetic and molecular anomalies have been identified in FDCS. It often carries an aberrant clonal karyotype and chromosomal structural alterations, frequently involving onco-suppressor genes. Direct or next generation sequencing showed alterations on genes belonging to the NF-κB regulatory pathway and cell-cycle regulators. In contrast to hematopoietic-derived histiocytic and dendritic cells tumors, FDCS typically lacks mutations in genes related to the MAPK pathway. FDCS recurs locally in 28% and metastasizes in 27% of cases. Extent of the disease, surgical resectability and histopathological features are significantly associated with the outcome. IPT-like FDCS behaves as an indolent tumor, even if it often recurs locally over years. Complete surgical excision is the gold standard of treatment. Data on targeted therapies (e.g.: tyrosine kinase inhibitors) or immune checkpoint inhibitors are very limited and responses are variable. A better understanding of the molecular drivers of this tumor may lead to potential new therapeutic strategies.

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Section: Fdc In Hematological Disordersmentioning

confidence: 99%

Follicular dendritic cell sarcoma

2021

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“…Similarly, another group reported that Grade 3 FL exhibited a significant decrease of CD23 expression by the FDCs as compared with G1 FL, although CD21 expression was not significantly different [40]. Furthermore, Ohe et al reported that high estrogen receptor α expression on FDCs was an independent prognostic factor for OS and PFS in FL patients [41].…”

Section: Follicular Dendritic Cell Role In Healthy and Neoplastic Folliclesmentioning

confidence: 92%

The Tumor Microenvironment in Follicular Lymphoma: Its Pro-Malignancy Role with Therapeutic Potential

Watanabe

2021

IJMS

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In the follicular lymphoma (FL) microenvironment, CXCR5+ICOS+PD1+BCL6+ follicular helper T (Tfh) cells, which closely correlate with FL B cells in neoplastic follicles, play a major role in supporting FL. Interleukin-4 secreted by Tfh cells triggers the upregulation of the lymphocyte chemoattractant CXCL12 in stromal cell precursors, in particular by fibroblastic reticular cells (FRCs). In turn, mesenchymal fistromal cells (MSCs) can be committed to FRC differentiation in the bone marrow and lymph nodes involved by FL. Noteworthy, MSCs can promote the differentiation of Tfh cells into highly immunosuppressive T-follicular regulatory cells. The tumor suppressor HVEM is highly mutated in FL cells, and its deficiency increases Tfh cell frequency. In contrast, PI3Kδ inhibition impedes the recruitment of Tfh/regulatory T cells and impairs the proliferation of follicular dendritic cells (FDCs) and FDC-induced angiogenesis. Since TIGIT ligands are expressed by FDCs, the immune checkpoint receptor TIGIT plays an important role in tumor-infiltrating T cells. Thus, TIGIT blockade might invigorate cytotoxic T cells in the FL microenvironment. Given their potential to simultaneously reduce the neoplastic B cells, Tfh, and TFR cells could also reinforce the effects of the cytotoxic T cells. This combinatory strategy should be explored as a treatment option to tackle FL.

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Molecular Biomarkers in Prediction of High-Grade Transformation and Outcome in Patients with Follicular Lymphoma: A Comprehensive Systemic Review

Enemark,

Hemmingsen,

Jensen

et al. 2024

IJMS

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Follicular lymphoma (FL) is the most prevalent indolent B-cell lymphoma entity, often characterized by the t(14;18) BCL2-IGH translocation. The malignancy represents a clinically and biologically highly heterogeneous disease. Most patients have favorable prognoses; however, despite therapeutic advancements, the disease remains incurable, with recurrent relapses or early disease progression. Moreover, transformation to an aggressive histology, most often diffuse large-B-cell lymphoma, remains a critical event in the disease course, which is associated with poor outcomes. Understanding the individual patient’s risk of transformation remains challenging, which has motivated much research on novel biomarkers within the past four decades. This review systematically assessed the research on molecular biomarkers in FL transformation and outcome. Following the PRISMA guidelines for systemic reviews, the PubMed database was searched for English articles published from January 1984 through September 2024, yielding 6769 results. The identified publications were carefully screened and reviewed, of which 283 original papers met the inclusion criteria. The included studies focused on investigating molecular biomarkers as predictors of transformation or as prognostic markers of time-related endpoints (survival, progression, etc.). The effects of each biomarker were categorized based on their impact on prognosis or risk of transformation as none, favorable, or inferior. The biomarkers included genetic abnormalities, gene expression, microRNAs, markers of B cells/FL tumor cells, markers of the tumor microenvironment, and soluble biomarkers. This comprehensive review provides an overview of the research conducted in the past four decades, underscoring the persistent challenge in risk anticipation of FL patients.

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Good prognosis for follicular lymphoma with estrogen receptor α‐positive follicular dendritic cells

Cited by 4 publications

References 28 publications

Follicular dendritic cell sarcoma

Follicular dendritic cell sarcoma

The Tumor Microenvironment in Follicular Lymphoma: Its Pro-Malignancy Role with Therapeutic Potential

Molecular Biomarkers in Prediction of High-Grade Transformation and Outcome in Patients with Follicular Lymphoma: A Comprehensive Systemic Review

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