Cellular Senescence in Cancer: Biomarkers, Immune Crosstalk, and Therapeutic Targeting

Cellular senescence occupies a pivotal position in cancer biology, acting as both a barrier against malignant transformation and a potential driver of disease progression. As a multifaceted stress response, senescence involves enduring proliferative arrest and profound changes in cellular secretion and metabolism, collectively reshaping the tumor microenvironment. Recent studies have underscored the complexity of therapy-induced senescence, which can be triggered in malignant, stromal, and even immune cells by diverse anticancer interventions, including chemotherapy, radiotherapy, targeted agents, and CDK4/6 inhibitors. Rather than uniformly halting disease, therapy-induced senescence may promote stemness, immune evasion, and microenvironmental remodeling through the senescence-associated secretory phenotype (SASP), challenging long-held assumptions about its unambiguously tumor-suppressive role. Significant knowledge gaps remain regarding the context-dependent duality of senescence, the mechanisms by which SASP mediates both immune clearance and immune suppression, and the impact of senescent cells on minimal residual disease, recurrence, and the efficacy of immunotherapy.

This Research Topic aims to unify mechanistic and translational insights on cellular senescence in cancer, with a focus on its interplay with the immune system and therapeutic outcomes. We seek to dissect how senescence manifests and dynamically evolves across distinct cell types and treatment contexts, identifying when and where it is protective versus detrimental. Special emphasis is placed on clarifying the cell-intrinsic and microenvironmental factors that regulate senescence induction, maintenance, and immune-mediated elimination or persistence. Additionally, we aim to foster advances in the development of robust biomarkers to detect and monitor senescence, and in strategizing therapeutically actionable approaches, including targeted senolytics, senomorphics, and rational immunotherapy combinations, to harness or mitigate senescence in a precision medicine framework.

The scope of this Research Topic encompasses fundamental, translational, and clinical investigations into senescence and its immune crosstalk across the cancer continuum, spanning early, residual, and advanced disease stages. We encourage submissions that address, but are not confined to, the following themes:

- Comparative characterization of senescence programs in tumor versus stromal and immune compartments and their distinct consequences.

- Determinants and dynamics of therapy-induced senescence, including its reversibility, escape mechanisms, and correlation with therapeutic resistance.

- Molecular biology of SASP: its roles in immune recruitment or suppression, pro-metastatic niche formation, and systemic effects.

- Biomarker development: immunohistochemistry, multiplex panels, transcriptomic/proteomic signatures, circulating markers, extracellular vesicles, and secretome analyses.

- Spatial and single-cell methodologies to map senescence and immune interactions in situ.

- Mechanisms of senescence-driven immune evasion or clearance, and their relevance for immunotherapy response.

- The efficacy, mechanisms, and safety of senolytics and senomorphics—alone or in rational combinations with established therapies.

- Clinical trial strategies for senescence modulation: design, patient stratification, endpoints, and monitoring.

- Disease settings, including early lesions, post-neoadjuvant residual disease, metastatic progression, and recurrence risk.





Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases that are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of the scope of this Research Topic.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Senescence, SASP, tumor microenvironment, immune crosstalk, immunotherapy, senolytics, senomorphics

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.