Abstract 294: A novel cancer therapeutic strategy: inducing cytotoxic functions in tumor-associated macrophages

Macrophages are recognized as an important component of the tumor microenvironment. Previous studies have shown that they promote tumor growth and participate in the initiation and progression of metastatic spread. Methods are being developed to eliminate macrophages from the tumor, thereby inhibiting their negative effects. However, we believe that the best approach would be to transform the tumor-helping macrophages into tumor-killing macrophages that would both eliminate tumor cells directly and re-invigorate other immune cells around them to better fight the tumor. Our data indicates that we have found a way to induce this transformation.We utilized a novel transgenic mouse model to determine the effects of activating Nuclear Factor Kappa-B (NF-κB) signaling specifically in macrophages in vivo during different stages of tumor progression. Our data shows that activated macrophages not only inhibit primary tumor growth but also reduce tumor cell seeding and colonization of distant organs, such as the lung. This is accomplished at least in part through direct tumor cell killing by the macrophages. We have further modeled this mechanism in vitro through co-culture assays of macrophages and a variety of tumor cell lines, including breast, ovarian, and melanoma. In each case, activation of NF-κB in macrophages induces a tumoricidal phenotype, in which macrophages directly attack the tumor cells significantly depleting them by three days of co-culture. Having established macro...

Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Barham, W., Tikhomirov, O., Ortega, R., Saskowski, J., Thompson, C. S., Wilson, A., Blackwell, T., Mirafzali, Z., Khabele, D., Giorgio, T., Yull, F. E. Tags: Immunology Source Type: research