Taking a Swing at TIMP1-Armed Immunosuppressive Astrocytes Unleashes T cell Immunity against Brain Metastases

Priego and colleagues identify a secreted glycoprotein TIMP1, expressed downstream of the transcription factor STAT3, in a subpopulation of STAT3+ reactive astrocytes as a mediator of immunosuppression in late-stage brain metastases. The STAT3 inhibitor silibinin enhances the preclinical efficacy of the combined PD-1/CTLA4 immune checkpoint blockade, providing a rationale to translate the combination therapy into clinical use for this underserved patient group with poor prognosis.