1. Academic Validation
  2. Lymphoma accelerates T cell and tissue aging

Lymphoma accelerates T cell and tissue aging

  • Cancer Cell. 2025 Aug 18:S1535-6108(25)00329-0. doi: 10.1016/j.ccell.2025.07.023.
Rebecca S Hesterberg 1 Joshua T Davis 2 Komal J Handoo 3 Aya G Elmarsafawi 3 Anthony C Augello 3 Chia-Ho Cheng 4 Reginald Atkins 5 Dae Hyun Lee 6 Chunying Yang 3 Jiqiang Yao 4 Krishna R Patel 3 Melanie Mediavilla-Varela 7 Javier Pinilla-Ibarz 7 Carolina Soto-Palma 8 Frederick L Locke 5 Xiaofei Song 2 Xuefeng Wang 2 Anders E Berglund 9 Paulo C Rodriguez 10 Gero Knittel 11 Ruth Flümann 12 Hans Christian Reinhardt 13 Timothy I Shaw 2 Xiaoqing Yu 2 Laura J Niedernhofer 8 John L Cleveland 14
Affiliations

Affiliations

  • 1 Department of Tumor Microenvironment & Metastasis, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. Electronic address: rebecca.hesterberg@moffitt.org.
  • 2 Department of Biostatistics and Bioinformatics, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
  • 3 Department of Tumor Microenvironment & Metastasis, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
  • 4 Biostatistics & Bioinformatics Shared Resource, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
  • 5 Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
  • 6 Department of Internal Medicine, Division of Cardiovascular Disease, University of South Florida, Tampa, FL 33602, USA.
  • 7 Department of Malignant Hematology, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
  • 8 Institute on the Biology of Aging & Metabolism, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
  • 9 Department of Biostatistics and Bioinformatics, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL 32224, USA.
  • 10 Department of Immunology, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
  • 11 Department of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany; West German Cancer Center, University Hospital Essen, Essen, Germany; DKTK Partner Site Essen/Düsseldorf, University Hospital Essen, Essen, Germany; Center for Molecular Biotechnology, University Hospital Essen, Essen, Germany.
  • 12 Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • 13 Department of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany; West German Cancer Center, University Hospital Essen, Essen, Germany; DKTK Partner Site Essen/Düsseldorf, University Hospital Essen, Essen, Germany; Center for Molecular Biotechnology, University Hospital Essen, Essen, Germany; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • 14 Department of Tumor Microenvironment & Metastasis, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. Electronic address: john.cleveland@moffitt.org.
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.

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