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Where the immune cells sit matters: triple-negative tumours with killer T cells inside the tumour did well, tumours with no T cells and fibrotic B7-H4-rich stroma did badly, and a third group kept T cells trapped in the stroma with PD-L1 on stromal cells.
Spatial resolution of immune cells was integrated with laser-capture microdissection expression profiles of tumour and stroma. Immunoreactive TNBCs had tumoural granzyme B-positive CD8 T cells, a type 1 interferon signature and elevated IDO and PD-L1, with good outcome. An immune-cold microenvironment lacking tumoural CD8 cells was defined by high B7-H4, fibrotic stroma signatures and poor outcome. A distinct poor-outcome immunomodulatory microenvironment showed stromal restriction of CD8 cells, stromal PD-L1 and cholesterol biosynthesis signatures. Metasignatures stratified TNBC outcome and suggested targets.
It explains why a PD-L1 score alone predicts imperfectly: PD-L1 on stromal cells with excluded T cells is a poor-outcome pattern, and B7-H4 marks the cold tumours now being targeted by antibody-drug conjugates.
Shares Cold tumours: immune deserts and exclusion, Tumour microenvironment (TME), Tumour-infiltrating lymphocytes (TILs), PD-L1.
Shares Tumour-infiltrating lymphocytes (TILs), Digital pathology & AI, Triple-negative breast cancer (TNBC).
Shares Tumour microenvironment (TME), Triple-negative breast cancer (TNBC).
Shares Cold tumours: immune deserts and exclusion, Tumour microenvironment (TME), Tumour-infiltrating lymphocytes (TILs).
Shares Tumour-infiltrating lymphocytes (TILs), Triple-negative breast cancer (TNBC).