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Published on: November 28, 2019
Macrophage-mediated bystander effect triggered by tumor cell apoptosis
Yinghui Huang1, Casey Lee, Per Borgström
1Sidney Kimmel Cancer Center, San Diego, California, USA.
Cancer treatments that induce apoptosis can be enhanced by bystander effects, particularly involving macrophages. Macrophages, activated by apoptotic tumor cells, amplify the therapeutic impact of cancer treatments.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Restoring apoptosis is a key cancer therapy strategy.
- Bystander effects, where one cell's death triggers another's, may significantly impact treatment outcomes.
- The role of macrophages in mediating these bystander effects in cancer treatment is not fully understood.
Purpose of the Study:
- To investigate the role of bystander effects in pro-apoptotic cancer treatments.
- To determine the involvement of macrophages in mediating bystander apoptosis.
- To explore the mechanisms by which macrophages contribute to bystander effects.
Main Methods:
- Utilized a murine N202 breast cancer chamber model.
- Employed intravital microscopy to observe cellular interactions in vivo.
- Conducted in vitro co-culture experiments with N202 cells, modified N202 cells (overexpressing p14ARF), and macrophages.
Main Results:
- Observed bystander apoptosis in vivo in mixed N202 cell spheroids.
- Bystander apoptosis was not observed in vitro or transferable via conditioned medium.
- Inclusion of macrophages in vitro restored bystander apoptosis, correlating with increased phosphatidyl serine expression on modified N202 cells.
- Macrophage-mediated bystander killing was specific to apoptotic tumor cells and not observed with less efficient chemotherapy agents (cisplatin, 5-fluorouracil).
Conclusions:
- Pro-apoptotic cancer therapies are enhanced by bystander effects.
- Macrophages play a crucial role in amplifying therapeutic efficacy through bystander apoptosis.
- The innate immune response, specifically macrophage activation by apoptotic tumor cells, is essential for maximizing the benefits of pro-apoptotic cancer treatments.
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