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Cellular Senescence, Aging and the Tumor Microenvironment in Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: 28 February 2027 | Viewed by 424

Special Issue Editors


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Guest Editor
Department of Anatomical Pathology, Singapore general Hospital, Singapore Duke-University Medical School, Singapore
Interests: senescence; tumor microenvironment; immune biomarkers

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Guest Editor Assistant
Division of Pathology, Singapore General Hospital, Singapore
Interests: computational biology; bioinformatics; cancer immunology; AI

Special Issue Information

Dear Colleagues,

Immunosenescence, the age-related decline in immune function, significantly worsens cancer progression and limits therapeutic success in older adults. Driven by hallmarks like genomic instability, telomere attrition, mitochondrial dysfunction, and chronic inflammation, this process fosters a tumor-promoting microenvironment (TME). Aging reshapes the TME through the recruitment of immunosuppressive cells and the release of senescence-associated secretory phenotypes (SASP), leading to therapy resistance and a poor prognosis.

While immunotherapies such as immune checkpoint inhibitors (ICIs) and CAR-T cell therapy offer promise, their efficacy is hampered in the elderly by factors like T cell exhaustion and myeloid bias. Emerging rejuvenation strategies, including senolytics, epigenetic modulators (like HDAC inhibitors), and metabolic interventions (spermidine, NMN), offer potential to restore aged immunity.

Single-cell multiomics provides deep insights into immune cell heterogeneity, revealing novel targets like IL-34 for inflammation. Addressing immunosenescence is crucial. Future efforts demand age-tailored clinical trials and biomarker-driven approaches to optimize precision oncology for the aging population.

This Special Issue aims to invite papers on the following subtopics:

Subtopics to highlight in the call:

  • Therapy-induced senescence and SASP;
  • Senescent cells in the TME (stromal, immune, endothelial);
  • Aging, immunosenescence, and cancer immunotherapy;
  • Senolytics and cancer prevention/treatment;
  • Biomarkers of cellular and organismal aging in cancer;
  • Age-related health disparities in cancer outcomes.

Diverse paper types are invited:

  • Basic mechanistic studies;
  • Translational biomarker research;
  • Clinical trials and retrospective analyses;
  • Reviews and perspectives;
  • Methodological papers.

In this Special Issue, original research articles and reviews are welcome. We look forward to receiving your contributions.

Dr. Jabed Iqbal  
Guest Editor

Dr. Jeremy Wee Kiat Ng
Guest Editor Assistant

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • aging
  • senescence
  • immunosenescence
  • SASP
  • tumor microenvironment
  • immunotherapy

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Published Papers (1 paper)

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Research

15 pages, 1224 KB  
Article
Paquinimod Targeting of the S100A8/A9 Axis Suppresses Liver Metastasis in Aged Mice
by Takao Tsuneki, Masafumi Saito, Kimihiro Yamashita, Masayuki Ando, Keisuke Yasuda, Naoto Shirakami, Ryota Ito, Yukari Adachi, Hiroki Kagiyama, Takaaki Tachibana, Masaki Imai, Sachiko Inubushi, Kazuki Kanayama, Yu-Ichiro Koma, Mitsugu Fujita, Joerg-Matthias Pollok, Yutaka Sugita, Taro Ikeda, Yasufumi Koterazawa, Tomoaki Aoki, Hitoshi Harada, Yasunori Otowa, Naoki Urakawa, Hironobu Goto, Hiroshi Hasegawa, Shingo Kanaji, Takeru Matsuda and Yoshihiro Kakejiadd Show full author list remove Hide full author list
Cancers 2026, 18(10), 1635; https://doi.org/10.3390/cancers18101635 - 19 May 2026
Viewed by 144
Abstract
Background: Aging profoundly alters host immunity, yet how age-associated immune changes in the liver influence the growth of metastatic tumors remains incompletely understood. Liver metastasis is a major cause of cancer-related mortality, particularly in elderly patients, for whom aggressive treatments are often [...] Read more.
Background: Aging profoundly alters host immunity, yet how age-associated immune changes in the liver influence the growth of metastatic tumors remains incompletely understood. Liver metastasis is a major cause of cancer-related mortality, particularly in elderly patients, for whom aggressive treatments are often not feasible. This study aimed to clarify how aging reshapes the hepatic immune microenvironment and to identify age-associated host factors that influence liver metastasis growth. Methods: Tumor-naïve and tumor-bearing young and aged mice were analyzed using a syngeneic MC38 liver metastasis model. Immune cell composition in the liver was assessed by flow cytometry, and gene expression was evaluated by quantitative reverse transcription PCR (RT–qPCR). Public transcriptomic datasets were screened to identify age-associated inflammatory factors. The functional relevance of the S100A8/A9 axis was examined using the small-molecule inhibitor paquinimod. Results: Aging was associated with a distinct baseline immune cell composition in the liver. During liver metastasis, overall growth was comparable between young and aged mice; however, metastatic lesions in aged hosts showed increased expression of multiple inflammation-related genes and prominent accumulation of Ly6G+ cells. In silico screening identified S100a9 as one of the most highly upregulated inflammation-related genes in aged livers, which was confirmed in both tumor-naïve and metastatic liver tissues. Pharmacological modulation of the S100A8/A9 axis with paquinimod significantly reduced liver metastasis growth in aged, but not young, mice, and was accompanied by a shift in immune cell composition, including an increased representation of CD8+ T cells. Conclusions: These findings indicate that aging is associated with a distinct hepatic immune context that shapes the inflammatory and cellular composition of the tumor microenvironment during liver metastasis. S100A9 emerges as a key age-associated, host-derived factor that is functionally relevant to the growth of liver metastases in aged hosts, supporting the S100A8/A9 axis as a context-specific therapeutic target. Full article
(This article belongs to the Special Issue Cellular Senescence, Aging and the Tumor Microenvironment in Cancer)
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