Lymphoma accelerates T cell and tissue aging

IF 44.5 1区医学 Q1 CELL BIOLOGY

Cancer Cell Pub Date : 2025-08-21 DOI:10.1016/j.ccell.2025.07.023

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

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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.

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淋巴瘤加速T细胞和组织老化

研究人员在携带B细胞淋巴瘤的年轻和老年小鼠以及来自年轻和老年B细胞淋巴瘤患者的T细胞中研究了衰老和癌症对免疫细胞的综合影响。这些分析表明，淋巴瘤本身足以触发年轻T细胞的转录、表观遗传和表型改变，这些改变在老年T细胞中表现出来。相反，衰老的T细胞对淋巴瘤引起的变化有很大的抵抗力。通路分析显示，开放的染色质区域和控制铁稳态的基因都是由淋巴瘤和衰老诱导的，淋巴瘤经历和衰老的T细胞有增加的铁池，并对铁凋亡具有抗性。此外，衰老和淋巴瘤经历的T细胞都有蛋白质平衡缺陷。B细胞淋巴瘤还会加速其他组织的衰老，Cdkn2a和Tnfa的表达升高就是证据。最后，一些淋巴瘤引起的衰老表型是可逆的，而另一些是固定的，这表明有机会改善一些癌症相关的衰老合并症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell 医学-肿瘤学

CiteScore

55.20

自引率

1.20%

发文量

179

审稿时长

4-8 weeks

期刊介绍： Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.