Oral Presentation 29th Lorne Cancer Conference 2017

Tumor-initiating cells cannot form secondary tumors in the presence of an interleukin-1 mediated inflammatory response to the primary tumor (#16)

Christine L Chaffer 1 2 , Zafira Castano 3 , Robert A Weinberg 1 , Sandra S McAllister 3
  1. Whitehead Institute for Biomedical Research, Camridge
  2. Garvan Institute of Biomedical Research, Sydney, NSW, Australia
  3. Harvard Medical School, Boston, MA, USA

Current lack of insight into mechanisms governing breast cancer metastasis precludes development of curative therapies. Tumor-initiating cells (TICs) are cancer cells that are uniquely equipped to establish metastases and thought to account for disease recurrence and therapeutic resistance. Using models of early metastatic disease, we have uncovered mechanisms by which certain primary tumors can prevent distant TICs from generating secondary tumors. The inhibitory primary tumors secrete IL-1a, which elicits a systemic innate immune response involving IL-1b-expressing monocytes that infiltrate the distant TIC microenvironment. IL-1b is sufficient to maintain TICs in a mesenchymal, non-proliferative state that prevents them from giving rise to differentiated, proliferative epithelial progeny that are critical for forming robustly growing tumor tissue. IL-1R inhibition or surgical resection of the inhibitory primary tumor permits outgrowth of TIC-derived secondary tumors. These results suggest opportunities for developing better risk assessment algorithms and therapeutic interventions that could be administered before lethal metastatic disease erupts.