This article details a comprehensive study of Pituitary Neuroendocrine Tumors (PitNETs) using integrated single-cell RNA sequencing and spatial transcriptomics to understand tumor heterogeneity and progression. The research analyzes over 177,000 cells across 57 tissue samples, identifying distinct tumor populations and characterizing the reconfiguration of the tumor microenvironment (TME). Key findings include the identification of an aggressive tumor cluster (ACTHAgg) associated with elevated p53-mediated proliferation and a higher Trouillas classification, and the enrichment of SPP1+ tumor associated macrophages (TAMs) in invasive tumors. These TAMs facilitate invasion through the SPP1-ITGAV/ITGB1 signaling pathway, which is explored through extensive in vitro validation using cell lines and organoid models. Ultimately, the paper suggests that these molecular dynamics within the TME offer potential targets for therapeutic intervention against aggressive PitNETs.

References:

• Su W, Ye Z, Liu J, et al. Single-cell and spatial transcriptome analyses reveal tumor heterogeneity and immune remodeling involved in pituitary neuroendocrine tumor progression[J]. Nature Communications, 2025, 16(1): 5007.