Reactive astrocytes foster brain metastases via STAT3 signaling

Braden C. McFarland, Etty N. Benveniste


Brain metastasis remains a grim and complicating factor in many cancers, regardless of the primary tumor origin (1). Moreover, the unique brain microenvironment inadvertently aides in brain metastasis growth and progression (2). In a recently published paper by Priego et al. (3), it was uncovered that there is a subpopulation of reactive astrocytes (RA) that surround brain metastases and are driven by signal transducer and activator of transcription 3 (STAT3) activation. The metastatic tumor cells in the brain secrete various factors that trigger astrocytes to become reactive and display enhanced STAT3 activation. These STAT3+ RA produce cytokines and other factors that inhibit an appropriate anti-tumor immune response. Both innate and adaptive immune functions are compromised due to the activities of these STAT3+ RA. Targeting the STAT3 signaling pathway in the microenvironment helps reduce pro-tumorigenic signaling and decreases brain metastasis burden.