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Across 1,512 triple-negative tumours each molecular subtype had its own immune landscape: the immunomodulatory type is fully inflamed and suited to checkpoint drugs, while basal-like, LAR and mesenchymal tumours are immune-cold with the T cells kept at the margin.
Tumour microenvironment heterogeneity was investigated within each TNBC molecular subtype, including immune infiltrate localisation and composition and expression of targetable immune pathways, in public transcriptomic and genomic datasets totalling 1,512 samples. Each subtype exhibited distinct profiles of immune, vascularisation, stroma and metabolism processes. The immunomodulatory subtype had the highest adaptive immune signatures and a fully inflamed spatial pattern; most mesenchymal stem-like and LAR tumours were immunosuppressive with high stromal signatures; basal-like, LAR and mesenchymal subtypes showed an immune-cold, margin-restricted phenotype. Tumours with high chromosomal instability and copy-number loss on 5q and 15q, including MHC-related genes, showed reduced cytotoxic activity as a plausible immune escape mechanism.
It links the Lehmann subtypes to the spatial immune classes of Gruosso and gives a rationale for pairing checkpoint inhibitors with the immunomodulatory subtype and stromal or metabolic agents with the cold ones.
Shares Cold tumours: immune deserts and exclusion, Tumour microenvironment (TME), Tumour-infiltrating lymphocytes (TILs), PD-L1.
Shares Tumour microenvironment (TME), Triple-negative breast cancer (TNBC).
Shares Antigen presentation & immune editing, PD-L1, Triple-negative breast cancer (TNBC).
Shares Tumour-infiltrating lymphocytes (TILs), Triple-negative breast cancer (TNBC).
Shares Cold tumours: immune deserts and exclusion, Tumour microenvironment (TME), Tumour-infiltrating lymphocytes (TILs).
Shares Antigen presentation & immune editing, Tumour microenvironment (TME).