This article explores how triple-negative breast cancer (TNBC) responds to a combination of pembrolizumab and radiation therapy through advanced single-cell and spatial profiling. By analyzing patient biopsies over time, the authors identified 12 distinct spatial districts and three specific response trajectories among patients. While some individuals showed an immediate immune response, a second group only achieved a significant clinical benefit after the addition of radiation. Conversely, non-responders remained immunologically inactive throughout the treatment, often characterized by low MHC expression. The study suggests that radiation can bridge the gap for certain patients by inducing antigen-presenting macrophages and expanding effector T cells. Ultimately, these findings provide a framework for using spatial biomarkers to personalize immunotherapy and improve survival in difficult-to-treat cancers.

References:

• Shiao SL, Knott SRV. Single-cell and spatial profiling identify three response trajectories to pembrolizumab and radiation therapy in triple negative breast cancer. Cancer Cell. 2024 Jan 8;42(1):70-84.e8. doi: 10.1016/j.ccell.2023.12.012. PMID: 38194915.