Senescent cells in cancer immunity: mechanisms of immune remodeling and opportunities for traditional Chinese medicine-derived senotherapeutics
Abstract
Cellular senescence has context-dependent effects in cancer. Although transient senescence can suppress malignant proliferation, persistent senescent cells in the tumor microenvironment (TME) may promote tumor progression, immune escape and treatment resistance. How these cells reshape antitumor immunity, and whether traditional Chinese medicine (TCM)-derived interventions can target them, has not been integrated within a translational framework. This Review synthesizes the immune-regulatory activities of pre-existing senescent cells in the TME through three interconnected mechanisms: cell-autonomous immune evasion caused by altered activating and inhibitory surface signals; senescence-associated secretory phenotype (SASP)-driven recruitment and reprogramming of immunosuppressive myeloid and lymphoid populations; and immunosenescence-associated failure of senescent-cell surveillance. We then evaluate TCM-derived natural products and formulas according to their predominant effects on established senescent cells: senomorphic suppression of harmful SASP programs, senolytic elimination of senescent cells, and emerging immune-oriented strategies designed to restore the recognition and clearance of senescent cells. Reductions in SASP-associated inflammation and paracrine tumor support are the most consistently supported endpoints across compounds and experimental models. Evidence linking senolysis to immune remodeling remains limited, whereas immune-mediated clearance has been explored only in preliminary preclinical studies. Across these categories, heterogeneous senescent cell states, inconsistent biomarkers, limited immune-functional endpoints and insufficient standardization of complex formulas constrain mechanistic interpretation and clinical translation. Persistent senescent cells evade immune clearance through altered surface recognition and SASP-mediated immune remodeling, while immunosenescence further weakens host surveillance. These mechanisms identify restoration of senescence surveillance as a therapeutic opportunity. Future studies should investigate TCM-derived natural products as a source of novel senotherapeutics capable of restoring immune recognition and clearance of pre-existing senescent cells, either alone or alongside senomorphic or senolytic activity. This immune-oriented strategy should be validated using direct measures of immune-cell engagement, senescent cell clearance and antitumor efficacy.
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BibTeX
@article{zhang2026senescent,
title = {{Senescent cells in cancer immunity: mechanisms of immune remodeling and opportunities for traditional Chinese medicine-derived senotherapeutics}},
author = {Qiuhua Zhang and Huimin Jin and Lingyong Cao and Fangfang Tao},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1977552},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1977552},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Senescent cells in cancer immunity: mechanisms of immune remodeling and opportunities for traditional Chinese medicine-derived senotherapeutics
AU - Qiuhua Zhang
AU - Huimin Jin
AU - Lingyong Cao
AU - Fangfang Tao
PY - 2026
DA - 2026/11/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1977552
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1977552
AB - Cellular senescence has context-dependent effects in cancer. Although transient senescence can suppress malignant proliferation, persistent senescent cells in the tumor microenvironment (TME) may promote tumor progression, immune escape and treatment resistance. How these cells reshape antitumor immunity, and whether traditional Chinese medicine (TCM)-derived interventions can target them, has not been integrated within a translational framework. This Review synthesizes the immune-regulatory activities of pre-existing senescent cells in the TME through three interconnected mechanisms: cell-autonomous immune evasion caused by altered activating and inhibitory surface signals; senescence-associated secretory phenotype (SASP)-driven recruitment and reprogramming of immunosuppressive myeloid and lymphoid populations; and immunosenescence-associated failure of senescent-cell surveillance. We then evaluate TCM-derived natural products and formulas according to their predominant effects on established senescent cells: senomorphic suppression of harmful SASP programs, senolytic elimination of senescent cells, and emerging immune-oriented strategies designed to restore the recognition and clearance of senescent cells. Reductions in SASP-associated inflammation and paracrine tumor support are the most consistently supported endpoints across compounds and experimental models. Evidence linking senolysis to immune remodeling remains limited, whereas immune-mediated clearance has been explored only in preliminary preclinical studies. Across these categories, heterogeneous senescent cell states, inconsistent biomarkers, limited immune-functional endpoints and insufficient standardization of complex formulas constrain mechanistic interpretation and clinical translation. Persistent senescent cells evade immune clearance through altered surface recognition and SASP-mediated immune remodeling, while immunosenescence further weakens host surveillance. These mechanisms identify restoration of senescence surveillance as a therapeutic opportunity. Future studies should investigate TCM-derived natural products as a source of novel senotherapeutics capable of restoring immune recognition and clearance of pre-existing senescent cells, either alone or alongside senomorphic or senolytic activity. This immune-oriented strategy should be validated using direct measures of immune-cell engagement, senescent cell clearance and antitumor efficacy.
SN - 1664-3224
ER -