Transforming Growth Factor-Beta Orchestrates Tumour and Bystander Cells in B-Cell Non-Hodgkin Lymphoma.

Autor: Timmins MA; Wellcome Trust/MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AH, UK.; Department of Haematology, Addenbrooke's Hospital, Cambridge University Hospital, Cambridge CB2 0AH, UK., Ringshausen I; Wellcome Trust/MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AH, UK.; Department of Haematology, Addenbrooke's Hospital, Cambridge University Hospital, Cambridge CB2 0AH, UK.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Mar 31; Vol. 14 (7). Date of Electronic Publication: 2022 Mar 31.
DOI: 10.3390/cancers14071772
Abstrakt: 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.
Databáze: MEDLINE
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