Graduate Student Expo 2011
Kathryn Wycislo, PhD/Clinical Pathology Residency candidate
Investigating the balance of TLR agonists in tumor of immune cells
Advisor: T. Fan
Osteosarcoma (OS) is the most common primary bone tumor in both humans and canines. Although many treatments for OS exist, most patients have micrometastases at the time of diagnosis and survival times with traditional chemotherapy have plateaued. Interestingly, studies have shown that human and canine cancer patients with secondary surgical infections live up to twice as long as those who do not experience infection. This suggests that tumor cells are immunogenic; however, most available immunotherapies focus on the adaptive arm of the immune system and cannot be directly used in canines. Investigation into optimizing the innate immune system for the treatment of OS, specifically through toll-like receptors (TLRs), is only within its infancy.
TLRs are a class of pattern-recognition receptors (PRRs) that recognize conserved molecular sequences of invading pathogens. The TLR signaling cascade centers upon the release of inflammatory cytokines and type 1 interferons via NF-κB and IRF. While considered a critical component of the innate immune system, TLRs are also vital for shaping appropriate adaptive responses. Current research into the use of TLR agonists has shown both pro-tumorigenic and anti-tumorigenic effects in various types of cancer, supporting the notion of a “balance” between TLR agonists within tumor and immune cells. This balance remains relatively uncharacterized in OS and will be the focus of this research project.