Assistant Professor Carnegie Mellon University, United States
Introduction:: Our knowledge of cancer pathogenesis has exponentially expanded cancer treatment strategies in a way that has created more personalized options but also more design complexity. In this talk, I will focus on monocytes and their use as a therapeutic cellular target for cancer nanotechnology. Monocytes are circulating innate immune cells that infiltrate solid tumors at surprisingly high rates, contribute to the immunosuppressive tumor microenvironment, and are correlated with poor therapeutic response outcomes. I will discuss two approaches that use data to design and evaluate cancer nanoformulations, 1) time-resolved quantitative tracking of monocyte polarization, and 2) machine learning guided literature synthesis. We hope the models developed will lead to enhanced prediction of translational efficacy and ultimately improved clinical outcomes.
Materials and Methods:: We present a novel bioluminescent method that allows for time-resolved measurement of NFᴋB activation in macrophages while in co-culture with cancer cells. By using a monocyte cell line whose NFᴋB responsive element is labeled with firefly luciferase, we obtain a quantitative and temporal characterization of macrophage polarization in response to tumor-derived signals. Bioluminescence measurements were taken of tumor:monocyte co-cultures to quantify the effect of tumor cell signaling on THP-1 monocyte and monocyte derived-macrophage NFᴋB activation.
We also synthesized literature from 2000-2020 to evaluate the most effective nanoparticle and therapeutic combination strategies for macrophage targeted cancer nanotechnologies.
Results, Conclusions, and Discussions:: We observed the MDA-MB-231 cancer cells induced lower NFᴋB activation in THP-1 monocyte derived macrophages than was observed in HCT-116 co-culture. The temporal trend in activation possessed different profiles. Moreover, the addition of macrophage differentiation stimuli modulated the NFᴋB profile in the co-culture, with PMA treated cells expressing higher NFᴋB activation. We propose that the difference in the NFᴋB profile is correlated with disease severity and should be pursued as a model.
