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@ARTICLE{Belenki:300198,
author = {D. Belenki and P. Richter-Pechanska and Z. Shao and A.
Bhattacharya and A. Lau and J. A. Nabuco Leva Ferreira de
Freitas and G. Kandler and T. P. Hick and X. Cai and E.
Scharnagl and A. Bittner and M. Schönlein and J. Kase and
K. Pardon and B. Brzezicha and N. Thiessen and O. Bischof
and J. R. Dörr and M. Reimann and M. Milanovic$^*$ and J.
Du and Y. Yu and B. Chapuy and S. Lee and U. Leser and C.
Scheidereit and J. Wolf and D. N. Y. Fan$^*$ and C. A.
Schmitt$^*$},
title = {{S}enescence-associated lineage-aberrant plasticity evokes
{T}-cell-mediated tumor control.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-00675},
pages = {3079},
year = {2025},
abstract = {Cellular senescence is a stress-inducible state switch
relevant in aging, tumorigenesis and cancer therapy. Beyond
a lasting arrest, senescent cells are characterized by
profound chromatin remodeling and transcriptional
reprogramming. We show here myeloid-skewed aberrant lineage
plasticity and its immunological ramifications in
therapy-induced senescence (TIS) of primary human and murine
B-cell lymphoma. We find myeloid transcription factor (TF)
networks, specifically AP-1-, C/EBPβ- and PU.1-governed
transcriptional programs, enriched in TIS but not in equally
chemotherapy-exposed senescence-incapable cancer cells.
Dependent on these master TF, TIS lymphoma cells adopt a
lineage-promiscuous state with properties of
monocytic-dendritic cell (DC) differentiation. TIS lymphoma
cells are preferentially lysed by T-cells in vitro, and mice
harboring DC-skewed Eμ-myc lymphoma experience
significantly longer tumor-free survival. Consistently,
superior long-term outcome is also achieved in diffuse large
B-cell lymphoma patients with high expression of a
TIS-related DC signature. In essence, these data demonstrate
a therapeutically exploitable, prognostically favorable
immunogenic role of senescence-dependent aberrant myeloid
plasticity in B-cell lymphoma.},
keywords = {Animals / Humans / Cellular Senescence: immunology /
Cellular Senescence: genetics / Mice / T-Lymphocytes:
immunology / Cell Lineage / Cell Differentiation / Dendritic
Cells: immunology / Cell Line, Tumor / Lymphoma, Large
B-Cell, Diffuse: immunology / Lymphoma, Large B-Cell,
Diffuse: genetics / Lymphoma, Large B-Cell, Diffuse:
pathology / Proto-Oncogene Proteins: metabolism /
Proto-Oncogene Proteins: genetics / CCAAT-Enhancer-Binding
Protein-beta: metabolism / CCAAT-Enhancer-Binding
Protein-beta: genetics / Gene Expression Regulation,
Neoplastic / Cell Plasticity / Transcription Factor AP-1:
metabolism / Mice, Inbred C57BL / Monocytes: immunology /
Monocytes: metabolism / Lymphoma, B-Cell: immunology /
Lymphoma, B-Cell: genetics / Female / Transcription Factors:
metabolism / Transcription Factors: genetics /
Trans-Activators / proto-oncogene protein Spi-1 (NLM
Chemicals) / Proto-Oncogene Proteins (NLM Chemicals) /
CCAAT-Enhancer-Binding Protein-beta (NLM Chemicals) /
Transcription Factor AP-1 (NLM Chemicals) / Transcription
Factors (NLM Chemicals) / Trans-Activators (NLM Chemicals)},
cin = {BE01},
ddc = {500},
cid = {I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40159497},
doi = {10.1038/s41467-025-57429-x},
url = {https://inrepo02.dkfz.de/record/300198},
}