期刊
CANCERS
卷 14, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/cancers14071772
关键词
TGFB; B-cell lymphoma; microenvironment
类别
资金
- Clinical Research Training Fellowship from the Cancer Research UK Cambridge Clinical Academic Training Award [C9685/A31312]
- Cancer Research UK Cambridge Centre [C49940/A25117]
- University of Cambridge Department of Haematology, Cambridge University Hospitals NHS Foundation Trust
- Wellcome Trust [203151/Z/16/Z]
- UKRI Medical Research Council [MC_PC_17230]
TGFB plays a crucial role in B-cell lymphoma, regulating the tumor microenvironment and facilitating bidirectional signaling between tumor cells. Research on TGFB signaling provides insights into disease pathogenesis and potential therapeutic strategies.
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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