Cancer Immunology, Inflammation & Immunotherapy Program
Assistant Professor, Biological Sciences
Georgia Cancer Center
2500 Walton Way, SCI C20207
My laboratory is currently exploring how immune signaling in myeloid cells affects breast cancer and glioblastoma, an extremely aggressive brain cancer.
Our laboratory focuses on the interactions between cancer cells and macrophages via the nuclear factor-kappaB (NF-κB) signaling pathway. NF-κB is a family of five transcription factors (RelA/p65, RelB, p50, p52, c-Rel) that form different dimers to regulate target gene expression in diverse biological functions, including normal immune function, synaptic plasticity, and even memory. Aberrant NF-κB activity is associated with autoimmune diseases and, importantly, cancer.
Our laboratory’s research efforts in the area of NF-κB signaling in glioblastoma (GBM) are part of a collaboration with Dr. Ali Arbab’s laboratory (Georgia Cancer Center). We have been using cell and animal models (NF-κB conditional knockout mice) to determine the role of myeloid NF-κB on GBM growth. We have found that stimulation of GBM cell lines with bone marrow-derived macrophage conditioned media from control cells, but not from cells lacking p65 (a canonical transcription factor), elevates GBM NF-κB signaling and increases stem cell properties. Recently, we have identified that conditional deletion of canonical NF-κB signaling in myeloid cells inhibits syngeneic GBM growth, decreases CD45 infiltration into tumors, and positively influences CD8+ T cell proliferation. These data suggest that canonical NF-κB signaling has an anti-inflammatory role and is required for macrophage polarization, immune suppression, and GBM growth. Combining a NF-κB signaling inhibitor with standard therapy could improve anti-tumor immunity in GBM.
Ongoing work in this area includes production and use of a conditional knockout model in which microglia will lack NF-κB signaling. This model will enable us to more clearly determine the role of the microglial NF-κB contribution in GBM.
Our laboratory also has an interest in stromal macrophage NF-κB signaling in breast cancer. NF-κB is known to be up-regulated in breast cancer subtypes that also have high numbers of infiltrating macrophages, which are called tumor associated macrophages (TAMs). TAMs are found in many types of cancer and can compose upwards of half of the total invasive breast cancer tumor mass, which is associated with poor prognosis. The basal and claudin-low subtypes of breast cancer are very aggressive and difficult to treat, and, interestingly, these subtypes are also associated with high macrophage infiltration. Microarray data indicate that NF-κB-dependent target genes are strongly up-regulated in basal-like and claudin-low breast cancers, which could be due to the large numbers of infiltrating macrophages. This finding, along with the fact that NF-κB can also regulate tumor stem cells, makes the issue of uncovering the role NF-κB communication between TAMs and breast cancer cells very important.
Current Undergraduate Researchers: