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Conquering aging-related immunosenescence and tumor immune escape

Shanshan Zhang1,2, Bo Yang3, Mingyi Xu1,2,4

  • 1Shandong Provincial Key Medical and Health Laboratory of Blood Ecology and Biointelligence, Science and Technology Innovation Center, The Fourth People's Hospital of Jinan Affiliated to Shandong Second Medical University, Jinan, China.

Frontiers in Immunology
|March 26, 2026
PubMed

Insights

Aging promotes cancer by altering cells and the immune system, hindering immunotherapy. Strategies like clearing senescent cells and modulating the senescence-associated secretory phenotype (SASP) may improve cancer treatment outcomes in older adults.

Area of Science:

  • Oncology
  • Immunology
  • Gerontology

Background:

  • Global population aging increases cancer incidence.
  • Cellular senescence and immunosenescence are key drivers of age-related tumorigenesis.
  • Aging impacts molecular pathways, immune surveillance, and tumor microenvironment.

Purpose of the Study:

  • To review mechanisms of tumor immune escape in aging.
  • To discuss strategies for improving cancer treatment efficacy in the elderly.
  • To highlight the role of senescence in cancer development and progression.

Main Methods:

  • Literature review of aging, senescence, and cancer immunology.
  • Analysis of molecular and cellular changes associated with aging.
  • Examination of the senescence-associated secretory phenotype (SASP) and its role in tumor immunity.

Main Results:

  • Aging-associated molecular changes (DNA damage, telomere shortening, epigenetic dysregulation) promote malignancy.
  • Immunosenescence and SASP create an immunosuppressive tumor microenvironment, favoring tumor escape.
  • Aging impairs antigen presentation, signaling pathways, and tumor suppressive functions, reducing immunotherapy efficacy in elderly patients.

Conclusions:

  • Senescence is a critical factor in age-related cancer development and immune evasion.
  • Targeting senescent cells and SASP offers potential therapeutic strategies.
  • Combination therapies hold promise for enhancing cancer treatment outcomes in aging populations.
Keywords:
SASPagingimmunosenescencetumor immune escapetumor microenvironment (TME)

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