Immune evasion of senescent cells: Mechanisms, pathological significance, and targeted interventions

Qikun Ou; Jinran Zhao; Yuanlong Ge; Shu Wu

doi:10.70401/acrt.2026.0034

Immune evasion of senescent cells: Mechanisms, pathological significance, and targeted interventions

Qikun Ou

Jinran Zhao

Yuanlong Ge

Shu Wu

1,*

Affiliation +

*Correspondence to: Shu Wu, Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong, China. E-mail: wushu@jnu.edu.cn

Ageing Cancer Res Treat. 2026;3:202617. 10.70401/acrt.2026.0034

Received: April 21, 2026Accepted: August 10, 2026Published: August 10, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Cellular senescence is a stress-induced cell-cycle arrest program accompanied by the senescence-associated secretory phenotype (SASP). While senescent cells are typically eliminated through immune surveillance under normal physiological conditions, they tend to accumulate progressively during aging and in chronic diseases. This review summarizes current evidence suggesting that such persistence is attributable not only to immune system decline but also to active, cell-intrinsic mechanisms of immune evasion. We discuss how senescent cells escape clearance by weakening immune recognition, suppressing phagocytic removal, resisting apoptosis, remodeling the inflammatory and structural microenvironment through SASP, and activating inhibitory checkpoint pathways in aged tissues. Furthermore, we investigate the contribution of these mechanisms to representative age-related diseases across multiple organs. Finally, we highlight emerging therapeutic strategies aimed at targeting the immune evasion of senescent cells, including checkpoint modulation, CAR-based cell therapies, vaccination approaches and other immune-bypass strategies. Collectively, these insights underscore immune evasion as a critical determinant of senescent cell persistence and a promising target for interventions in aging and age-related diseases.

Keywords

Cellular senescence, immune evasion, senescence surveillance, SASP, immunosenescence

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Ou Q, Zhao J, Ge Y, Wu S. Immune evasion of senescent cells: Mechanisms, pathological significance, and targeted interventions. Ageing Cancer Res Treat. 2026;3:202617. https://doi.org/10.70401/acrt.2026.0034