Lymphoma accelerates T cell and tissue aging

Rebecca S. Hesterberg; Joshua T. Davis; Komal J. Handoo; Aya G. Elmarsafawi; Anthony C. Augello; Chia Ho Cheng; Reginald Atkins; Dae Hyun Lee; Chunying Yang; Jiqiang Yao; Krishna R. Patel; Melanie Mediavilla-Varela; Javier Pinilla-Ibarz; Carolina Soto-Palma; Frederick L. Locke; Xiaofei Song; Xuefeng Wang; Anders E. Berglund; Paulo C. Rodriguez; Gero Knittel; Ruth Flümann; Hans Christian Reinhardt; Timothy I. Shaw; Xiaoqing Yu; Laura J. Niedernhofer; John L. Cleveland

doi:10.1016/j.ccell.2025.07.023

Lymphoma accelerates T cell and tissue aging

Rebecca S. Hesterberg
, Joshua T. Davis
, Komal J. Handoo
, Aya G. Elmarsafawi
, Anthony C. Augello
, Chia Ho Cheng
, Reginald Atkins
, Dae Hyun Lee
, Chunying Yang
, Jiqiang Yao
, Krishna R. Patel
, Melanie Mediavilla-Varela
, Javier Pinilla-Ibarz
, Carolina Soto-Palma
, Frederick L. Locke
, Xiaofei Song
, Xuefeng Wang
, Anders E. Berglund
, Paulo C. Rodriguez
, Gero Knittel

Ruth Flümann, Hans Christian Reinhardt, Timothy I. Shaw, Xiaoqing Yu, Laura J. Niedernhofer, John L. Cleveland

Biochemistry, Molecular Biology, and Biophysics (TMED)

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

The combined effects of aging and cancer on immune cells were investigated in young versus aged mice harboring B cell lymphoma, and in T cells from young and aged B cell lymphoma patients. These analyses revealed that lymphoma alone is sufficient to trigger transcriptional, epigenetic, and phenotypic alterations in young T cells that manifest in aged T cells. In contrast, aged T cells are largely resistant to lymphoma-induced changes. Pathway analyses revealed open chromatin regions and genes controlling iron homeostasis are induced by both lymphoma and aging, and lymphoma-experienced and aged T cells have increased iron pools and are resistant to ferroptosis. Furthermore, both aged and lymphoma-experienced T cells have defects in proteostasis. B cell lymphoma also accelerates aging of other tissues, as evidenced by elevated expression of Cdkn2a and Tnfa. Finally, some lymphoma-induced aging phenotypes are reversible whereas others are fixed, indicating opportunities for improving some cancer-associated aging comorbidities.

Original language	English (US)
Pages (from-to)	1917-1936.e8
Journal	Cancer Cell
Volume	43
Issue number	10
DOIs	https://doi.org/10.1016/j.ccell.2025.07.023
State	Published - Oct 13 2025

Bibliographical note

Publisher Copyright:
© 2025 The Authors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

B cell lymphoma
NK cell
T cell
aging
ferroptosis

PubMed: MeSH publication types

Journal Article

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10.1016/j.ccell.2025.07.023

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Hesterberg, R. S., Davis, J. T., Handoo, K. J., Elmarsafawi, A. G., Augello, A. C., Cheng, C. H., Atkins, R., Lee, D. H., Yang, C., Yao, J., Patel, K. R., Mediavilla-Varela, M., Pinilla-Ibarz, J., Soto-Palma, C., Locke, F. L., Song, X., Wang, X., Berglund, A. E., Rodriguez, P. C., ... Cleveland, J. L. (2025). Lymphoma accelerates T cell and tissue aging. Cancer Cell, 43(10), 1917-1936.e8. https://doi.org/10.1016/j.ccell.2025.07.023

Hesterberg, RS, Davis, JT, Handoo, KJ, Elmarsafawi, AG, Augello, AC, Cheng, CH, Atkins, R, Lee, DH, Yang, C, Yao, J, Patel, KR, Mediavilla-Varela, M, Pinilla-Ibarz, J, Soto-Palma, C, Locke, FL, Song, X, Wang, X, Berglund, AE, Rodriguez, PC, Knittel, G, Flümann, R, Reinhardt, HC, Shaw, TI, Yu, X, Niedernhofer, LJ & Cleveland, JL 2025, 'Lymphoma accelerates T cell and tissue aging', Cancer Cell, vol. 43, no. 10, pp. 1917-1936.e8. https://doi.org/10.1016/j.ccell.2025.07.023

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title = "Lymphoma accelerates T cell and tissue aging",

abstract = "The combined effects of aging and cancer on immune cells were investigated in young versus aged mice harboring B cell lymphoma, and in T cells from young and aged B cell lymphoma patients. These analyses revealed that lymphoma alone is sufficient to trigger transcriptional, epigenetic, and phenotypic alterations in young T cells that manifest in aged T cells. In contrast, aged T cells are largely resistant to lymphoma-induced changes. Pathway analyses revealed open chromatin regions and genes controlling iron homeostasis are induced by both lymphoma and aging, and lymphoma-experienced and aged T cells have increased iron pools and are resistant to ferroptosis. Furthermore, both aged and lymphoma-experienced T cells have defects in proteostasis. B cell lymphoma also accelerates aging of other tissues, as evidenced by elevated expression of Cdkn2a and Tnfa. Finally, some lymphoma-induced aging phenotypes are reversible whereas others are fixed, indicating opportunities for improving some cancer-associated aging comorbidities.",

keywords = "B cell lymphoma, NK cell, T cell, aging, ferroptosis",

author = "Hesterberg, \{Rebecca S.\} and Davis, \{Joshua T.\} and Handoo, \{Komal J.\} and Elmarsafawi, \{Aya G.\} and Augello, \{Anthony C.\} and Cheng, \{Chia Ho\} and Reginald Atkins and Lee, \{Dae Hyun\} and Chunying Yang and Jiqiang Yao and Patel, \{Krishna R.\} and Melanie Mediavilla-Varela and Javier Pinilla-Ibarz and Carolina Soto-Palma and Locke, \{Frederick L.\} and Xiaofei Song and Xuefeng Wang and Berglund, \{Anders E.\} and Rodriguez, \{Paulo C.\} and Gero Knittel and Ruth Fl{\"u}mann and Reinhardt, \{Hans Christian\} and Shaw, \{Timothy I.\} and Xiaoqing Yu and Niedernhofer, \{Laura J.\} and Cleveland, \{John L.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

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month = oct,

day = "13",

doi = "10.1016/j.ccell.2025.07.023",

language = "English (US)",

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T1 - Lymphoma accelerates T cell and tissue aging

AU - Hesterberg, Rebecca S.

AU - Davis, Joshua T.

AU - Handoo, Komal J.

AU - Elmarsafawi, Aya G.

AU - Augello, Anthony C.

AU - Cheng, Chia Ho

AU - Atkins, Reginald

AU - Lee, Dae Hyun

AU - Yang, Chunying

AU - Yao, Jiqiang

AU - Patel, Krishna R.

AU - Mediavilla-Varela, Melanie

AU - Pinilla-Ibarz, Javier

AU - Soto-Palma, Carolina

AU - Locke, Frederick L.

AU - Song, Xiaofei

AU - Wang, Xuefeng

AU - Berglund, Anders E.

AU - Rodriguez, Paulo C.

AU - Knittel, Gero

AU - Flümann, Ruth

AU - Reinhardt, Hans Christian

AU - Shaw, Timothy I.

AU - Yu, Xiaoqing

AU - Niedernhofer, Laura J.

AU - Cleveland, John L.

PY - 2025/10/13

Y1 - 2025/10/13

N2 - The combined effects of aging and cancer on immune cells were investigated in young versus aged mice harboring B cell lymphoma, and in T cells from young and aged B cell lymphoma patients. These analyses revealed that lymphoma alone is sufficient to trigger transcriptional, epigenetic, and phenotypic alterations in young T cells that manifest in aged T cells. In contrast, aged T cells are largely resistant to lymphoma-induced changes. Pathway analyses revealed open chromatin regions and genes controlling iron homeostasis are induced by both lymphoma and aging, and lymphoma-experienced and aged T cells have increased iron pools and are resistant to ferroptosis. Furthermore, both aged and lymphoma-experienced T cells have defects in proteostasis. B cell lymphoma also accelerates aging of other tissues, as evidenced by elevated expression of Cdkn2a and Tnfa. Finally, some lymphoma-induced aging phenotypes are reversible whereas others are fixed, indicating opportunities for improving some cancer-associated aging comorbidities.

AB - The combined effects of aging and cancer on immune cells were investigated in young versus aged mice harboring B cell lymphoma, and in T cells from young and aged B cell lymphoma patients. These analyses revealed that lymphoma alone is sufficient to trigger transcriptional, epigenetic, and phenotypic alterations in young T cells that manifest in aged T cells. In contrast, aged T cells are largely resistant to lymphoma-induced changes. Pathway analyses revealed open chromatin regions and genes controlling iron homeostasis are induced by both lymphoma and aging, and lymphoma-experienced and aged T cells have increased iron pools and are resistant to ferroptosis. Furthermore, both aged and lymphoma-experienced T cells have defects in proteostasis. B cell lymphoma also accelerates aging of other tissues, as evidenced by elevated expression of Cdkn2a and Tnfa. Finally, some lymphoma-induced aging phenotypes are reversible whereas others are fixed, indicating opportunities for improving some cancer-associated aging comorbidities.

KW - B cell lymphoma

KW - NK cell

KW - T cell

KW - aging

KW - ferroptosis

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UR - https://www.scopus.com/pages/publications/105014024327#tab=citedBy

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SN - 1535-6108

VL - 43

SP - 1917-1936.e8

JO - Cancer Cell

JF - Cancer Cell

IS - 10

ER -

Lymphoma accelerates T cell and tissue aging

Abstract

Bibliographical note

UN SDGs

Keywords

PubMed: MeSH publication types

Publisher link

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