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Immunoregulatory mechanisms in the aging microenvironment: Targeting the senescence-associated secretory phenotype for cancer immunotherapy

Haojun Wang, Yang Yu, Runze Li, Huiru Zhang, Zhe‐Sheng Chen, Changgang Sun, Jing Zhuang

2025Acta Pharmaceutica Sinica B10 citationsDOIOpen Access PDF

Abstract

B, cGAS-STING, and mTOR, which regulate the expression of immune-related molecules (such as PD-L1) and promote the recruitment of immunosuppressive cells, including regulatory T cells and myeloid-derived suppressor cells. This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment. Furthermore, the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms, including approaches to inhibit SASP secretion or eliminate senescent cells. Although these strategies have shown promise in certain tumor models, the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies. This highlights the need for further research into adaptive stratification and personalized treatment approaches. Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.

Topics & Concepts

Paracrine signallingImmune systemCancer immunotherapyPhenotypeImmunotherapySuppressorBiologySenescenceCarcinogenesisCancer researchSignal transductionSecretionImmunologySignallingCell signalingCancerStimulus (psychology)Mechanism (biology)Cell biologyCancer cellTumor microenvironmentImmune toleranceAcquired immune systemReprogrammingImmune cells in cancerTelomeres, Telomerase, and SenescenceNeutrophil, Myeloperoxidase and Oxidative Mechanisms
Immunoregulatory mechanisms in the aging microenvironment: Targeting the senescence-associated secretory phenotype for cancer immunotherapy | Litcius