The three barriers senescent tumor cells must overcome to relapse
1Tulane School of Medicine, Department of Biochemistry and Molecular Biology, 1430 Tulane Avenue, mail code 8643, New Orleans, LA 70112.
Abstract:
Tumor cells that enter senescence as a response to treatment can be permanently arrested or removed by the immune system, resulting in a favorable patient outcomes. Alternatively, many studies have now shown that, in some tumors, the senescent program enables tumor cell survival, persistence, and eventually relapse, resulting in poor patient outcomes. Whether senescence is a positive or negative factor is dependent on whether on a clonal population of cells overcomes three critical barriers. First, senescence must enable survival from the initial stress of treatment, such as DNA damage, by preventing apoptosis and/or mitotic catastrophe. Senescent cells are also frequently immunogenic, thus, a second barrier is the activation of programs of immune evasion, such as PD-L1 expression, that outweigh the immunogenic properties. Third, senescent cells must escape their rigid arrest to proliferate again. Studies over the years have experimentally addressed challenging questions related to relapse and senescence, but more research is needed, particularly in vivo. Here, we discuss critical studies investigating how tumor cells that enter senescence as a response to treatment overcome barriers to relapse.
Insights
Tumor cells entering senescence can lead to favorable outcomes or relapse. Overcoming barriers like immune evasion and escaping arrest determines if senescence promotes tumor cell survival and poor patient prognosis.
Area of Science:
- Oncology
- Cellular Biology
- Immunology
Background:
- Tumor cells undergoing senescence can result in either tumor elimination or relapse.
- The role of senescence in cancer treatment outcomes is context-dependent.
- Senescence-induced tumor cell persistence is linked to poor patient prognosis.
Purpose of the Study:
- To review critical studies on how tumor cells overcome senescence-induced barriers.
- To discuss the mechanisms by which senescent tumor cells promote relapse.
- To highlight the importance of in vivo research in understanding senescence and relapse.
Main Methods:
- Review of existing experimental studies investigating tumor cell senescence.
- Analysis of mechanisms of senescence-induced survival, immune evasion, and proliferation.
- Discussion of barriers that senescent tumor cells must overcome to cause relapse.
Main Results:
- Senescence can promote tumor cell survival by preventing apoptosis and mitotic catastrophe.
- Immune evasion mechanisms, such as PD-L1 expression, can override the immunogenicity of senescent cells.
- Senescent cells must escape their arrest to proliferate, leading to tumor relapse.
Conclusions:
- The balance between senescence-induced tumor cell death and survival dictates patient outcomes.
- Understanding the barriers to relapse is crucial for developing effective cancer therapies.
- Further in vivo studies are needed to fully elucidate the role of senescence in tumor relapse.
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