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Updated: Dec 17, 2025
Simultaneous Imaging and Flow-Cytometry-based Detection of Multiple Fluorescent Senescence Markers in Therapy-Induced Senescent Cancer Cells
Published on: July 12, 2022
Senescence in the Development and Response to Cancer with Immunotherapy: A Double-Edged Sword
Anthony M Battram1, Mireia Bachiller1, Beatriz Martín-Antonio1,2
1Department of Hematology, Hospital Clinic, IDIBAPS, 08036 Barcelona, Spain.
Abstract:
Cellular senescence was first described as a physiological tumor cell suppressor mechanism that leads to cell growth arrest with production of the senescence-associated secretory phenotype known as SASP. The main role of SASP in physiological conditions is to attract immune cells to clear senescent cells avoiding tumor development. However, senescence can be damage-associated and, depending on the nature of these stimuli, additional types of senescence have been described. In the context of cancer, damage-associated senescence has been described as a consequence of chemotherapy treatments that were initially thought of as a tumor suppressor mechanism. However, in certain contexts, senescence after chemotherapy can promote cancer progression, especially when immune cells become senescent and cannot clear senescent tumor cells. Moreover, aging itself leads to continuous inflammaging and immunosenescence which are responsible for rewiring immune cells to become defective in their functionality. Here, we define different types of senescence, pathways that activate them, and functions of SASP in these events. Additionally, we describe the role of senescence in cancer and its treatments, including how aging and chemotherapy contribute to senescence in tumor cells, before focusing on immune cell senescence and its role in cancer. Finally, we discuss potential therapeutic interventions to reverse cell senescence.
Insights
Cellular senescence, a growth arrest process, can suppress tumors but also promote cancer. This review explores senescence types, SASP, and its dual role in cancer, aging, and treatment, discussing therapeutic reversal.
Area of Science:
- Cellular and Molecular Biology
- Immunology
- Oncology
Background:
- Cellular senescence, characterized by growth arrest and SASP, was initially viewed as a tumor suppressor mechanism.
- Damage-associated senescence, induced by stimuli like chemotherapy, presents a complex role in cancer progression.
- Aging contributes to inflammaging and immunosenescence, impairing immune surveillance and potentially promoting cancer.
Purpose of the Study:
- To define diverse senescence types and their activating pathways.
- To elucidate the functions of the senescence-associated secretory phenotype (SASP).
- To analyze the multifaceted role of senescence in cancer, treatment, and aging, focusing on immune cell senescence.
Main Methods:
- Literature review and synthesis of existing research on cellular senescence.
- Analysis of pathways activating different senescence types.
- Examination of SASP functions in physiological and pathological contexts.
Main Results:
- Senescence can act as both a tumor suppressor and a promoter of cancer progression, particularly after chemotherapy.
- Chemotherapy-induced senescence can paradoxically enhance cancer if immune cells are also senescent.
- Aging-related immunosenescence compromises the immune system's ability to clear senescent cells, potentially fueling cancer.
Conclusions:
- Senescence is a complex biological process with context-dependent roles in cancer.
- Understanding senescence in tumor and immune cells is crucial for cancer treatment strategies.
- Therapeutic interventions targeting senescence reversal hold promise for cancer therapy.
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