Senescence-associated lineage-aberrant plasticity evokes T-cell-mediated tumor control

Dimitri Belenki, Paulina Richter-Pechanska, Zhiting Shao, Animesh Bhattacharya, Andrea Lau, José Américo Nabuco Leva Ferreira de Freitas, Gregor Kandler, Timon P. Hick, Xiurong Cai, Eva Scharnagl, Aitomi Bittner, Martin Schönlein, Julia Kase, Katharina Pardon, Bernadette Brzezicha, Nina Thiessen, Oliver Bischof, Jan R. Dörr, Maurice Reimann, Maja Milanovic, Jing Du, Yong Yu, Björn Chapuy, Soyoung Lee, Ulf Leser, Claus Scheidereit, Jana Wolf, Dorothy N. Y. Fan and Clemens A. Schmitt ()
Additional contact information
Dimitri Belenki: Campus Virchow Klinikum
Paulina Richter-Pechanska: Campus Virchow Klinikum
Zhiting Shao: Campus Virchow Klinikum
Animesh Bhattacharya: Campus Virchow Klinikum
Andrea Lau: Campus Virchow Klinikum
José Américo Nabuco Leva Ferreira de Freitas: Faculté de Médecine de Créteil
Gregor Kandler: Campus Virchow Klinikum
Timon P. Hick: Campus Virchow Klinikum
Xiurong Cai: Campus Virchow Klinikum
Eva Scharnagl: Medical Faculty
Aitomi Bittner: Campus Virchow Klinikum
Martin Schönlein: Campus Virchow Klinikum
Julia Kase: Campus Virchow Klinikum
Katharina Pardon: Campus Virchow Klinikum
Bernadette Brzezicha: Experimental Pharmacology & Oncology Berlin-Buch GmbH
Nina Thiessen: Berlin Institute of Health
Oliver Bischof: Faculté de Médecine de Créteil
Jan R. Dörr: Campus Virchow Klinikum
Maurice Reimann: Campus Virchow Klinikum
Maja Milanovic: Campus Virchow Klinikum
Jing Du: Medical Research Center and Department of Oncology Binzhou Medical University Hospital
Yong Yu: Medical Faculty
Björn Chapuy: Campus Benjamin Franklin
Soyoung Lee: Campus Virchow Klinikum
Ulf Leser: Humboldt-Universität zu Berlin
Claus Scheidereit: Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Jana Wolf: Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Dorothy N. Y. Fan: Campus Virchow Klinikum
Clemens A. Schmitt: Campus Virchow Klinikum

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-57429-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57429-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-57429-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().