Transforming Growth Factor-Beta Orchestrates Tumour and Bystander Cells in B-Cell Non-Hodgkin Lymphoma
1
Wellcome Trust/MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AH, UK
2
Department of Haematology, Addenbrooke’s Hospital, Cambridge University Hospital, Cambridge CB2 0AH, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Franck Verrecchia
Cancers 2022, 14(7), 1772; https://doi.org/10.3390/cancers14071772
Received: 14 March 2022
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Accepted: 23 March 2022
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Published: 31 March 2022
(This article belongs to the Special Issue Feature Paper from Journal Reviewers)
Simple Summary
Transforming growth factor-beta (TGFB) is a ubiquitously expressed cytokine involved in numerous functions in both normal and cancer cells. Here, we review, for the first time, the evidence of how B-cell lymphoma cells respond to TGFB and utilise TGFB to modulate surrounding cells in the microenvironment. We highlight recent data supporting the bi-directional signalling between B-cell lymphoma cells and their microenvironment. Targeting TGFB signalling in B-cell lymphoma may provide a future therapeutic strategy but further research is required to understand how lymphoma cells interact in different microenvironmental contexts.
Transforming growth factor-beta (TGFB) is a critical regulator of normal haematopoiesis. Dysregulation of the TGFB pathway is associated with numerous haematological malignancies including myelofibrosis, acute myeloid leukaemia, and lymphoid disorders. TGFB has classically been seen as a negative regulator of proliferation in haematopoiesis whilst stimulating differentiation and apoptosis, as required to maintain homeostasis. Tumours frequently develop intrinsic resistant mechanisms to homeostatic TGFB signalling to antagonise its tumour-suppressive functions. Furthermore, elevated levels of TGFB enhance pathogenesis through modulation of the immune system and tumour microenvironment. Here, we review recent advances in the understanding of TGFB signalling in B-cell malignancies with a focus on the tumour microenvironment. Malignant B-cells harbour subtype-specific alterations in TGFB signalling elements including downregulation of surface receptors, modulation of SMAD signalling proteins, as well as genetic and epigenetic aberrations. Microenvironmental TGFB generates a protumoural niche reprogramming stromal, natural killer (NK), and T-cells. Increasingly, evidence points to complex bi-directional cross-talk between cells of the microenvironment and malignant B-cells. A greater understanding of intercellular communication and the context-specific nature of TGFB signalling may provide further insight into disease pathogenesis and future therapeutic strategies.
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Keywords:
TGFB; B-cell lymphoma; microenvironment
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MDPI and ACS Style
Timmins, M.A.; Ringshausen, I. Transforming Growth Factor-Beta Orchestrates Tumour and Bystander Cells in B-Cell Non-Hodgkin Lymphoma. Cancers 2022, 14, 1772. https://doi.org/10.3390/cancers14071772
AMA Style
Timmins MA, Ringshausen I. Transforming Growth Factor-Beta Orchestrates Tumour and Bystander Cells in B-Cell Non-Hodgkin Lymphoma. Cancers. 2022; 14(7):1772. https://doi.org/10.3390/cancers14071772
Chicago/Turabian StyleTimmins, Matthew A., and Ingo Ringshausen. 2022. "Transforming Growth Factor-Beta Orchestrates Tumour and Bystander Cells in B-Cell Non-Hodgkin Lymphoma" Cancers 14, no. 7: 1772. https://doi.org/10.3390/cancers14071772
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