03015: The Immune and Molecular Landscape of Canine Osteosarcoma at the Single-Cell Level

One Health: Yes

Abstract

The focus of this project is bone cancer (osteosarcoma), and the results will be especially relevant to large and giant dog breeds, and to mixed breed dogs with these breeds in their ancestry. Large dogs have an elevated risk to develop osteosarcoma, but there is little information available that can predict the speed at which the disease will progress or help guide treatment. Until recently, the prevailing dogma was that the immune system either ignored or was excluded from bone tumors. Using sensitive genomic methods, investigators showed that dogs (and children) that have immune cells present in their tumor survive longer than dogs (and children) where immune cells remain outside of their tumor. This is part of a growing body of evidence indicating that the immune system plays an important role in combating this disease. Two important questions regarding the role of the immune system in bone cancer remain unanswered: 1) “What is the precise identity of the immune cells that enter the tumor and benefit the patient?” and 2) “Where in the tumor do those cells need to be located to achieve this potential benefit?” By answering these questions, this project will inform the development of tests to guide treatment as well as new treatments to activate or enhance anti-tumor immune responses. The hypothesis is that bone tumors are segregated into 'neighborhoods' where productive anti-tumor immune responses are most likely to be initiated and sustained. Investigators will establish the extent to which tumor cells have followed separate evolutionary paths and created different subpopulations with unique behavior and susceptibility or resistance to treatment. They will identify, quantify, and characterize the diverse constituents of the bone cancer microenvironment (tumor cells, immune cells, supporting cells) at single-cell resolution, defining the 3-dimensional, spatial relationship of the cells in the bone cancer microenvironment using advanced methods. The 3-dimensional maps generated will help determine if and how immune cells are able to penetrate regions where the cancer cells reside, or if they are compartmentalized or excluded from these spaces. This project is the first to apply these technologies to bone cancer, and the information gained will further advance our understanding of how bone tumors form, aiding in earlier detection and prevention strategies.

Publication(s)

None at this time.