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Updated: Aug 18, 2025
Simultaneous Imaging and Flow-Cytometry-based Detection of Multiple Fluorescent Senescence Markers in Therapy-Induced Senescent Cancer Cells
Published on: July 12, 2022
Autophagy inhibition signals through senescence to promote tumor suppression
Nanfang Peng1, Helen H Kang1,2, Yan Feng1
1Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract:
Macroautophagy/autophagy, a stress-responsive cellular survival mechanism, plays important and context-dependent roles in cancer, and its inhibition has been implicated as a promising cancer therapeutic approach. The detailed mechanisms underlying the function of autophagy in cancer have not been fully understood. In this study, we show that autophagy inhibition promotes both the efficacy of chemotherapy for the treatment of glioblastoma (GBM) and therapy-induced senescence of GBM cells. As a specific cell fate characterized by permanent cell cycle arrest, senescence is also associated with the expression of a panel of specific secreted protein factors known as senescence-associated secretory phenotype (SASP). Intriguingly, we found that autophagy inhibition not only quantitatively enhanced GBM cell senescence but also qualitatively altered the spectrum of SASP. The altered SASP had increased potent activity to induce paracrine senescence of neighboring GBM cells, to skew macrophage polarization toward the anti-tumor M1 state, and to block the recruitment of pro-tumor neutrophils to GBM tumor tissues. Taken together, this study reveals novel functional communication between autophagy and senescence and suggests cancer therapeutic approaches harnessing autophagy blockage in inducing senescence-mediated antitumor immunity.
Insights
Inhibiting autophagy in glioblastoma (GBM) enhances chemotherapy and induces senescence. This senescence boosts anti-tumor immunity by altering the senescence-associated secretory phenotype (SASP).
Area of Science:
- Cancer biology
- Cellular stress responses
- Immunotherapy
Background:
- Macroautophagy/autophagy is a stress-responsive survival mechanism with context-dependent roles in cancer.
- Autophagy inhibition is a potential cancer therapeutic strategy, but its precise mechanisms in cancer remain unclear.
- Therapy-induced senescence, characterized by cell cycle arrest and the senescence-associated secretory phenotype (SASP), is a key cellular response.
Purpose of the Study:
- To investigate the role of autophagy inhibition in glioblastoma (GBM) treatment.
- To elucidate the functional communication between autophagy and senescence in GBM.
- To explore the potential of autophagy blockade in inducing senescence-mediated anti-tumor immunity.
Main Methods:
- Studied the effects of autophagy inhibition on chemotherapy efficacy in glioblastoma.
- Analyzed therapy-induced senescence and the senescence-associated secretory phenotype (SASP) in GBM cells.
- Assessed the impact of altered SASP on paracrine senescence, macrophage polarization, and neutrophil recruitment.
Main Results:
- Autophagy inhibition enhanced chemotherapy efficacy and induced senescence in GBM cells.
- Autophagy inhibition quantitatively increased GBM cell senescence and qualitatively altered the SASP.
- The altered SASP exhibited enhanced activity in inducing paracrine senescence, promoting M1 anti-tumor macrophage polarization, and inhibiting pro-tumor neutrophil recruitment.
Conclusions:
- Autophagy inhibition is a viable strategy to enhance GBM chemotherapy and induce potent anti-tumor senescence.
- A novel functional link between autophagy and senescence in cancer was revealed.
- Harnessing autophagy blockade to induce senescence-mediated anti-tumor immunity presents a promising therapeutic avenue for glioblastoma.
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