Recent clinical successes with check-point inhibitors and immuno-oncology agents have demonstrated the importance of the immune system in controlling and treating cancers. The rapid series of new drug approvals in diverse tumors ranging from lung cancer, to melanoma, to bladder cancer and to Hodgkin lymphoma show that the anti-tumor immune responses can be activated for therapeutic benefit.
However, our understanding of the mechanics of immune response to immuno-oncology agents has lagged behind the clinical successes. Furthermore, responses to immuno-oncology agents are not universal and mechanisms of resistance are poorly described. In large part, this is due to limitations of currently available imaging technology. In this proposal, we will develop a novel imaging technique known as imaging mass cytometry (IMC) to study tumor cell heterogeneity and its correlation with immune cells in the TME. IMC allows for highly multiplexed imaging of tissues similar to IHC but with 40+ parameters.
In our first years of Ming Hsieh funding we established the feasibility of using IMC to study immune cells in normal lymph node and Hodgkin lymphoma. Here we propose to develop a complete immuno-profiling panel that is broadly applicable to many different immuno-oncology agents and tumor types. We will then apply this panel to study a novel immuno-oncology agent, sEphB4-HSA, that is currently in clinical developed at the USC Norris Cancer Center.