2023 World Conference on Lung Cancer (Posters)-P1.04. Ablative Radiation Induces Distinct Sequential Waves of Mitotic and Innate Immune Death Regulated through DNA Repair Pathways

P1.04. Ablative Radiation Induces Distinct Sequential Waves of Mitotic and Innate Immune Death Regulated through DNA Repair Pathways - PDF(Abstract)

Back to course

Pdf Summary

This presentation at the WCLC 2023 conference focused on the molecular mechanisms of cell death induced by ablative radiation therapy (ART) and its potential synergy with immunotherapy. The researchers subjected various cell lines to different doses of radiation and analyzed the outcomes using live cell imaging and biochemical assays. They found that ART doses triggered two distinct waves of cell death. The first wave occurred 24-48 hours after treatment in cells irradiated in the S- or G2-phase of the cell cycle, dependent on intrinsic apoptosis. Homologous recombination (HR) played a role in promoting this wave of cell death. The second wave of cell death occurred days after ART in G1-phase irradiated cells, following at least one cell division with chromosome segregation errors. This wave was linked to non-homologous end joining and other DNA repair processes, leading to activation of the innate immune response through DNA/RNA sensing pathways and promoting extrinsic apoptosis. Abnormalities in the DNA repair pathways affected the outcomes of cell death, potentially influencing the efficacy of immunotherapy. Manipulating specific DNA repair pathways at key timings may enhance the synergy between ART and immunotherapy, suggesting a potential strategy for improving treatment outcomes.

Asset Subtitle

Harriet Gee

Meta Tag

Speaker Harriet Gee

Topic Tumor Biology: Preclinical Biology - Radiobiology

Keywords

molecular mechanisms

cell death

ablative radiation therapy

immunotherapy

radiation doses

live cell imaging

intrinsic apoptosis

homologous recombination

DNA repair processes

treatment outcomes