TY  - JOUR
AU  - Belenki, Dimitri
AU  - Richter-Pechanska, Paulina
AU  - Shao, Zhiting
AU  - Bhattacharya, Animesh
AU  - Lau, Andrea
AU  - Nabuco Leva Ferreira de Freitas, José Américo
AU  - Kandler, Gregor
AU  - Hick, Timon P
AU  - Cai, Xiurong
AU  - Scharnagl, Eva
AU  - Bittner, Aitomi
AU  - Schönlein, Martin
AU  - Kase, Julia
AU  - Pardon, Katharina
AU  - Brzezicha, Bernadette
AU  - Thiessen, Nina
AU  - Bischof, Oliver
AU  - Dörr, Jan R
AU  - Reimann, Maurice
AU  - Milanovic, Maja
AU  - Du, Jing
AU  - Yu, Yong
AU  - Chapuy, Björn
AU  - Lee, Soyoung
AU  - Leser, Ulf
AU  - Scheidereit, Claus
AU  - Wolf, Jana
AU  - Fan, Dorothy N Y
AU  - Schmitt, Clemens A
TI  - Senescence-associated lineage-aberrant plasticity evokes T-cell-mediated tumor control.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-00675
SP  - 3079
PY  - 2025
AB  - 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.
KW  - Animals
KW  - Humans
KW  - Cellular Senescence: immunology
KW  - Cellular Senescence: genetics
KW  - Mice
KW  - T-Lymphocytes: immunology
KW  - Cell Lineage
KW  - Cell Differentiation
KW  - Dendritic Cells: immunology
KW  - Cell Line, Tumor
KW  - Lymphoma, Large B-Cell, Diffuse: immunology
KW  - Lymphoma, Large B-Cell, Diffuse: genetics
KW  - Lymphoma, Large B-Cell, Diffuse: pathology
KW  - Proto-Oncogene Proteins: metabolism
KW  - Proto-Oncogene Proteins: genetics
KW  - CCAAT-Enhancer-Binding Protein-beta: metabolism
KW  - CCAAT-Enhancer-Binding Protein-beta: genetics
KW  - Gene Expression Regulation, Neoplastic
KW  - Cell Plasticity
KW  - Transcription Factor AP-1: metabolism
KW  - Mice, Inbred C57BL
KW  - Monocytes: immunology
KW  - Monocytes: metabolism
KW  - Lymphoma, B-Cell: immunology
KW  - Lymphoma, B-Cell: genetics
KW  - Female
KW  - Transcription Factors: metabolism
KW  - Transcription Factors: genetics
KW  - Trans-Activators
KW  - proto-oncogene protein Spi-1 (NLM Chemicals)
KW  - Proto-Oncogene Proteins (NLM Chemicals)
KW  - CCAAT-Enhancer-Binding Protein-beta (NLM Chemicals)
KW  - Transcription Factor AP-1 (NLM Chemicals)
KW  - Transcription Factors (NLM Chemicals)
KW  - Trans-Activators (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40159497
DO  - DOI:10.1038/s41467-025-57429-x
UR  - https://inrepo02.dkfz.de/record/300198
ER  -