IL-2 deprivation induces apoptosis in human IL-2-dependent T-cell clones. This process is characterized by typical cell morphology, changes in the cellular membranes and fragmentation of chromatin into units of single and multiple nucleosomes. We isolated apoptotic DNA of an IL-2-deprived T-cell clone and sequenced randomly selected fragments representing single and multiple nucleosomes.The frequency of phased adenosine tracts was markedly increased in the small apoptotic fragments as compared to oligonucleosomes. Our results thus indicate that chromatin fragmentation in human apoptotic T-cells is not random but preferentially involves DNA sequences with the capability to form bent DNA. Whether this indicates a colocalization of DNase cleavage sites and phased adenosine tracts on the chromosomes or a bias in selecting sites for apoptotic DNA fragmentation is discussed. Analysing the underlying mechanisms will shed new light on DNA degradation in apoptosis.
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Front Immunol
December 2024
Leeds Institute of Medical Research, School of Medicine, University of Leeds, St. James University Hospital, Leeds, United Kingdom.
Background: There has been limited success of cancer immunotherapies in the treatment of ovarian cancer (OvCa) to date, largely due to the immunosuppressive tumour microenvironment (TME). Tumour-associated macrophages (TAMs) are a major component of both the primary tumour and malignant ascites, promoting tumour growth, angiogenesis, metastasis, chemotherapy resistance and immunosuppression. Differential microRNA (miRNA) profiles have been implicated in the plasticity of TAMs.
View Article and Find Full Text PDFCancer Cell
December 2024
Pre-Cancer Immunology Laboratory, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK; Cancer Research UK Lung Cancer Centre of Excellence. Electronic address:
In this issue of Cancer Cell, Son et al. highlight an unexpected role for skin β-papillomaviruses in the protection against skin carcinogenesis. T cell immunity to skin papillomaviruses blocks the expansion of p53 mutant clones in ultraviolet (UV) radiation-damaged skin, preventing the development of skin cancer.
View Article and Find Full Text PDFPLoS One
January 2025
School of Information and Technology, Wenzhou Business College, Wenzhou, Zhejiang, China.
Liver cancer is the sixth most frequent malignancy and the fourth major cause of deaths worldwide. The current treatments are only effective in early stages of cancer. To overcome the therapeutic challenges and exploration of immunotherapeutic options, broad spectral therapeutic vaccines could have significant impact.
View Article and Find Full Text PDFBr J Haematol
January 2025
Department of Haematology, University College London Hospital, London, UK.
Systemic light chain (AL) amyloidosis is a rare clonal plasma cell disorder characterized by the production of amyloidogenic immunoglobulin light chains, which causes the formation and deposition of amyloid fibrils, leading to multi-organ dysfunction. Current treatment is directed at the underlying plasma cell clone to achieve a profound reduction in the monoclonal free light chain production. The standard-of-care first-line therapy is a combination of daratumumab, cyclophosphamide, bortezomib and dexamethasone (D-VCd regimen), resulting in high rates of haematological and organ responses.
View Article and Find Full Text PDFFront Immunol
January 2025
Dipartimento di Biomedicina e Prevenzione, Università di Roma Tor Vergata, Rome, Italy.
Background: Mature T-cell neoplasms arise from the neoplastic transformation of a single T lymphocyte, and all cells in a neoplastic clone share the same V segment in the beta chain of the T-cell receptor (TCR). These segments may represent an innovative target for the development of targeted therapies.
Methods: A specific V segment of the TCR beta chain (TRBV5-1) was analyzed using bioinformatic tools, identifying three potential antigenic peptides.
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