By Mallory Thompson

Faculty Mentor: Dr. Laura Sipe

Abstract

When cancer cells are treated with chemotherapy, they can die in a way that alerts and engages the immune system in order to initiate an immune response. This process is called an immunogenic cell death, or an ICD. The dying cancer cell can release or display certain molecules, including ATP and calreticulin, that immune cells recognize as abnormal and then initiate an anti-tumor response.
However, not all chemotherapies cause the release of these beneficial signals as they kill the cell. This study aims to determine whether a specific deprivation technique, called methionine restriction, promotes or initiates the immunogenic cell death process when used in conjunction with chemotherapy. Methionine is an amino acid that is integral to all protein synthesis. Thus, when methionine is restricted, we expect to see a larger concentration of immunogenic factors that could promote an immune response.
Breast cancer cells were incubated first with either methionine-restricted media or normal media before the addition of the chemotherapy cisplatin. The cells were then examined for overall death and signals for immunogenic cell death. In examining cell death, there was a significant increase in the proportion of dead cells treated with cisplatin and methionine restriction when compared to being treated with cisplatin alone. Additionally, there was a trending increase in ATP release when cells were treated with methionine restriction and cisplatin together as compared to baseline ATP release. The cells were also examined for calreticulin presence on the membrane. This experiment revealed a trending relationship where methionine restriction led to a larger presence of calreticulin on the membrane. This research supports the idea that methionine restriction could go to promote an immunogenic cell death, which could lead to a higher success rate of breast cancer treatment in patients.