Ana Luisa Correia, Champalimaud Foundation Lisbon

Harnessing neuron-NK cell interactions to prevent metastasis

The uncertainty of whether and when metastases will occur has been one of the most challenging factors in treatment effectiveness. In many cancer patients, persistent disseminated tumor cells (DTCs) enter a state of dormancy upon arrival at the distant tissue, only to awaken years or even decades afterwards and initiate deadly metastases. How cancer progresses from dormant to deadly metastatic is an outstanding question of utmost importance. My recent work revealed that the pool of natural killer (NK) cells within distant tissues can itself determine metastatic progression, and that normalizing NK cell abundance might be a way to effectively control dormant DTCs. But, what mechanisms control NK cell dynamics in tissues? Given that many neuroendocrine factors affect the number, activity and trafficking of NK cells, and metastatic progression coincides with exacerbated neuronal signaling, I hypothesized that neuronal hardwiring is a driver of NK cell dynamics in distant tissues. The Beug Foundation Metastasis Prize will allow me to comprehensively map tissue innervation and NK cell distribution during the formation of breast cancer metastases. This work will lay the basis for subsequent mechanistic and functional studies to explore neuron-NK cell interactions therapeutically to prevent metastatic seeds from ever sprouting.