By Mallory Thompson

Faculty Mentor: Dr. Laura Sipe

Abstract

When cancer cells are treated with chemotherapy, they can release Damage-Associated Molecular Patterns (DAMPs) as they die that can alert and engage the immune system, a process known as an immunogenic cell death (ICD). The dying cancer cell can release certain molecules, like ATP, that immune cells first recognize as abnormal before initiating 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, enhances the ICD process when used in conjunction with chemotherapy and to explore the cellular process through which it does so.

In this study on Triple Negative Breast Cancer murine cell line E0771, cells were first incubated with either methionine-restricted media or normal media before the addition of the chemotherapy cisplatin or oxaliplatin. 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 or oxaliplatin in conjunction with methionine restriction when compared to treatment with chemotherapy alone. There was a significant increase in ATP release per cell when treated with methionine-restricted media and oxaliplatin together when compared to baseline ATP release. Additionally, when autophagy was knocked down, we observed a decrease in ATP release per cell, suggesting that the autophagic pathway contributes to methionine restriction’s ability to promote an ICD. This research supports the idea that methionine restriction could go to promote an immunogenic cell death. Enhancing signals of an immunogenic cell death could increase the potency of chemotherapy by engaging the immune system, which could promote a lower relapse rate due to the currently limited TNBC treatment options available to patients.