By McKenzie Cheynet, Mohammad Ali Hassan, Evan Fisher

Faculty Mentor: Laura Sipe

Abstract

Some cancer treatments, such as specific chemotherapies, are immunogenic and can stimulate a robust immune response, while others fail to effectively engage the immune system. Enhancing the immunogenicity of chemotherapy is critical, not only to improve direct tumor cell killing but also to promote long-term immune surveillance that helps prevent recurrence. This immunogenicity is achieved through immunogenic cell death (ICD), a regulated form of apoptosis that leads to the release of damage-associated molecular patterns (DAMPs). These DAMPs serve as immune-stimulating signals that recruit and activate innate immune cells, including dendritic cells (DCs). While classical DAMPs like calreticulin and HMGB1 are well-characterized within ICD induction, the role of specific chemotherapies, such as oxaliplatin and cisplatin, in inducing ICD through type I interferon (IFN-I) release remains unclear.

This proposal investigates whether cisplatin and oxaliplatin induce ICD by triggering IFN-α secretion. Using EO771 murine mammary carcinoma cells, we assessed chemotherapy-induced apoptosis and IFN-I production in vitro to determine how each agent engages the innate immune response. Gene expression analysis of DC maturation markers, including CD11c, CXCL10, CD40, and CD86, was used to evaluate DC activation following chemotherapeutic treatment. Additionally, cytokine release following chemotherapy was analyzed via ELISA to better understand the role of IFN-α as a key mechanism driving ICD.

We hypothesize that cisplatin promotes IFN-α release as a key signal for DC activation during ICD. Confirming this will clarify how certain chemotherapeutic agents engage innate immunity to enhance anti-tumor responses, guiding strategies to improve cancer treatment outcomes by harnessing their immunogenic potential.