Follicular lymphoma (FL) is a generally incurable malignancy that originates from developmentally blocked germinal center B cells residing, primarily, within lymph nodes (LNs). During the long natural history of FL, malignant B cells often disseminate to multiple LNs and can affect virtually any organ. Nonmalignant LNs are highly organized structures distributed throughout the body, in which they perform functions critical for host defense. In FL, the malignant B cells “re-educate” the lymphoid environment by altering the phenotype, distribution, and abundance of other cells such as T cells, macrophages, and subsets of stromal cells. Consequently, dramatic anatomical changes occur and include alterations in the number, shape, and size of neoplastic follicles with an accompanying attenuation of the T-cell zone. Ongoing and dynamic interactions between FL B cells and the tumor microenvironment (TME) result in significant clinical heterogeneity observed both within and across patients. Over time, FL evolves into pathological variants associated with distinct outcomes, ranging from an indolent disease to more aggressive clinical courses with early death. Given the importance of both cell-intrinsic and -extrinsic factors in shaping disease progression and patient survival, comprehensive examination of FL tumors is critical. Here, we describe the cellular composition and architecture of normal and malignant human LNs and provide a broad overview of emerging technologies for deconstructing the FL TME at single-cell and spatial resolution. We additionally discuss the importance of capturing samples at landmark time points as well as longitudinally for clinical decision-making.
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THE INFLUENCE OF THE TUMOR MICROENVIRONMENT ON THE PATHOGENESIS OF B-CELL LYMPHOMAS|
March 21, 2024
The follicular lymphoma tumor microenvironment at single-cell and spatial resolution
Andrea J. Radtke,
Andrea J. Radtke
1Lymphocyte Biology Section and Center for Advanced Tissue Imaging, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Mark Roschewski
Mark Roschewski
2Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
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Blood (2024) 143 (12): 1069–1079.
Article history
Submitted:
October 19, 2023
Accepted:
December 17, 2023
First Edition:
January 9, 2024
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Citation
Andrea J. Radtke, Mark Roschewski; The follicular lymphoma tumor microenvironment at single-cell and spatial resolution. Blood 2024; 143 (12): 1069–1079. doi: https://doi.org/10.1182/blood.2023020999
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