A MOLECULAR UNDERSTANDING OF ANEUPLOID CELL CLEARANCE

Chromosome segregation errors can lead to aneuploidy, an abnormal chromosome number associated with cancer and genome instability. My Ph.D. research focused on understanding the interplay between aneuploid cells and the immune system. Utilizing mass spectrometry and the Surfaceome database, I investigated the plasma membrane differences between wild-type and NF-κB-depleted cells. The study revealed that the metastasis suppressor CD82 is overexpressed in NF-κB-competent aneuploid senescent cells, playing a crucial role in their recognition and elimination by Natural Killer cells. Additionally, DNA damage was found to trigger NF-κB activation and increase CD82 levels on the cell surface. In cancer and primary tumors, a positive correlation was observed between CD82 expression, NF-κB activation, and leukocyte infiltration. Clinical investigations demonstrated a favorable association between elevated initial CD82 levels and a full pathological response in triple-negative breast cancer patients undergoing chemotherapy and a fast-mimicking diet, known for its immune-enhancing properties. This discovery offers a promising tool for eradicating tumor cells and suggests innovative therapeutic strategies in cancer treatment. Beyond understanding aneuploidy's consequences, this research opens avenues for leveraging the immune system more efficiently in the battle against cancer.