Thesis Format

Integrated Article

Exploration of the Immune Landscape of EBV-associated Gastric Cancers

Mikhail Salnikov, Western UniversityFollow

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Mymryk, Joseph S.

Abstract

Epstein–Barr virus (EBV) is a gammaherpesvirus associated with 9% of all gastric cancers (GCs). EBV-associated GCs (EBVaGCs) are pathologically and clinically distinct entities from EBV-negative GCs (EBVnGCs), with EBVaGCs exhibiting differential molecular pathology and patient prognosis. The purpose of this thesis is to investigate the tumor microenvironment (TME) of EBVaGCs, which has not been explored in-depth. We hypothesize that EBVaGCs and EBVnGCs are also distinct in terms of the molecular immune landscape. We employed over 400 stomach adenocarcinoma (STAD) samples from The Cancer Genome Atlas (TCGA), as well as a single cell dataset, for the construction of a web suite of tools exploring multimodal data for GCs, and the exploration of changes in the TME of EBVaGCs and cellular phenotypes overrepresented in EBVaGCs. Our findings confirm the distinctness of EBVaGCs and EBVnGCs, with EBV-positive status possibly being a potential biomarker for the application of immunotherapy in GC.

Summary for Lay Audience

Epstein–Barr virus (EBV) is a virus that is responsible for 9% of gastric (stomach) cancer (GC) cases. GCs are the 5^th most common cancer and the 3^rd deadliest. GCs can be split into two distinct subgroups: EBV-positive (EBVaGCs) and EBV-negative (EBVnGCs), with EBVaGCs showing improved patient survival and different localization in the stomach. The purpose of this thesis is to explore the differences in the local immune system within the tumors of EBVaGCs and EBVnGCs, which has not been explored in-depth. To help with this, we designed a set of web tools employing large-scale data to help investigate the molecular differences between EBVaGCs and EBVnGCs. Using these tools, we were able to find differences, with EBVaGCs showing increased immune cell infiltration of the tumor, as well as unique cellular types present within the tumors as compared to EBVnGCs. Such findings will help identify new methods of treating EBVaGCs, thus improving patient survival.

Recommended Citation

Salnikov, Mikhail, "Exploration of the Immune Landscape of EBV-associated Gastric Cancers" (2023). Electronic Thesis and Dissertation Repository. 9450.
https://ir.lib.uwo.ca/etd/9450