Preventing Cancer Metastasis by T-Cells – UROP Spring Symposium 2022

Preventing Cancer Metastasis by T-Cells

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Emily Irish

Pronouns: she/her/hers

Research Mentor(s): Lonnie Shea
Co-Presenter:
Research Mentor School/College/Department: Biomedical Engineering / Engineering
Presentation Date: April 20
Presentation Type: Oral5
Session: Session 3 – 1:40pm – 2:30 pm
Room: Breakout Room 1
Authors: Emily Irish, Ian Schrack
Presenter: 5

Abstract

T-cells are valuable components of the immune system–exceptional when attacking viruses and most other aberrant cells–in order to protect the body. Yet T-cells fail to identify and eliminate cancerous cells for reasons that remain unclear. It is thought that these impaired T-cells have the potential to be engineered to restore immune function and ultimately aid in treating cancers. In order to open up the therapeutic possibilities of T-cells, the cancerous intercellular signaling networks driving T-cell immunosuppression must be explored. To do this, biological scaffolds, made of compressed polycaprolactone (PCL), a biodegradable polyester, are surgically implanted into breast cancer-bearing mice. Tumor cells from the mouse metastasize to both the lung, a natural metastatic tissue, and the scaffold. Secreted signaling factors from primary and metastatic tumors are collected at days 7, 14, and 21 post tumor-inoculation–early, intermediate, and late metastatic disease respectively. Paracrine signals from these explanted tissues and their influence on T cell behavior are explored through several T cell assays. To do this, the primary tumor and metastatic tissues (lung and scaffold) are explanted and processed to a single cell suspension and cultured for 24 hours. The supernatant is collected from culture and used for T cell assays to assess how secreted factors impact normal T cell functions, including proliferation, migration, and cytotoxicity. It was found that T cell proliferation initially decreases in response to early and intermediate metastatic signals but recovers to normal proliferation at late stage disease. Although this finding was initially surprising, it is believed this behavior is due to pro-tumor T cell subtypes being upregulated in late-stage disease. Future studies will investigate the phenotypes of proliferating T cells in response to metastatic signals to determine which cells are being enhanced in order to move toward the goal of restoring t-cell function in the presence of cancers.

Presentation link

Engineering, Interdisciplinary, Natural/Life Sciences

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