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Tumor CRATERs Flag T-Cell Killing Hotspots and Track With Immunotherapy Response

The Cell study identifies surface niches where CD8+ T cells linger, suggesting CRATER density could serve as a predictive marker pending clinical validation.

Overview

  • Live 3D imaging in transparent zebrafish revealed CD8+ T cells retained in discrete pockets on melanoma borders, named CRATERs.
  • Immunotherapy in the fish model expanded CRATER-covered surface area, increased local T cell localization, and coincided with more apoptosis within these zones.
  • High-resolution spatial transcriptomics showed elevated antigen-recognition molecules within CRATERs.
  • CRATER-like structures were observed in human melanoma and non–small cell lung cancer samples.
  • Patient samples with higher CRATER density were more likely to respond to checkpoint inhibitors, and the research team is planning a prospective trial to test clinical utility.