Investigating the role of the Immune Microenvironment in Esophageal Adenocarcinoma – UROP Spring Symposium 2021

Investigating the role of the Immune Microenvironment in Esophageal Adenocarcinoma

Rachel Anderson

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Pronouns: she/her/hers

Research Mentor(s): Kiran Lagisetty, Assistant Professor
Research Mentor School/College/Department: Department of Surgery, Michigan Medicine
Presentation Date: Thursday, April 22, 2021
Session: Session 6 (4pm-4:50pm)
Breakout Room: Room 10
Presenter: 1

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Abstract

Esophageal adenocarcinoma (EAC) develops from chronic inflammation, termed Barrett’s Esophagus (BE), that then progresses through stages of increasing dysplasia before tumor development at the esophagogastric junction. The impact of the EAC immune microenvironment on patient survival at each stage has yet to be fully understood. This study provides quantitative descriptions of immune populations in EAC and surrounding tissue and its correlation with survival. Core tissue samples showing varying stages of dysplasia to cancer were stained for the T-cell proteins CD3 (general T-cell marker), CD4 (memory T-cells), CD8 (cytotoxic T-cells) or FOXP3 (T-regulatory cells). T-cells remove foreign and cancerous cells from the body. Immune checkpoint proteins normally regulate the immune system and suppress overactivity. In cancer, these proteins promote tumor survival. Immune checkpoint therapy, inhibiting checkpoint suppression, has shown promise in treating certain cancers. Tissue samples were stained for immune checkpoint markers, CTLA4, TIGIT and PD1. Linear regression and correlation matrices compared the overall makeup of the different T-cell and immune checkpoint microenvironment populations during each stage of disease progression and relationships between these populations. Cancer cells were also treated with two cytokines, IL6 and IL8. Previous studies indicate that IL-6 promotes tumor cell survival through chemo-resistance. Results from this study aim to understand if IL-8, which we have shown is upregulated in EAC, acts similarly. The goal of this project is to better understand immune cell interactions with EAC tumors. Our hypothesis is that high concentrations of T-cells in dysplastic or cancerous tissue could indicate a positive patient response to immunotherapy.

Authors: Rachel Anderson, Dyke McEwen, Kiran Lagisetty
Research Method: Laboratory Research

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