{"entity":{"id":"paper-gruosso-tnbc-spatial-immune-microenvironments-jci-2019","kind":"paper","name":"Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-24","links":[{"label":"Gruosso et al., J Clin Invest 2019: spatially distinct immune microenvironments stratify TNBC","url":"https://doi.org/10.1172/JCI96313"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30753167/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["digital-pathology-ai"],"targets":["pdl1","b7h4","ido1"],"drugs":[],"companies":[],"institutions":[],"pathways":["immune-desert-exclusion","tumor-microenvironment"],"terms":["tils"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jci"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Investigation","year":2019,"doi":"10.1172/JCI96313","pmid":"30753167","authors":"Gruosso T, Gigoux M, Manem VSK, et al.","paperType":"translational","findings":["Three spatial immune classes: immunoreactive (good outcome), immune-cold with B7-H4 and fibrosis (poor), stroma-restricted with stromal PD-L1 (poor).","Metasignatures stratify outcome and nominate IDO, PD-L1 and B7-H4 as class-specific targets."],"whatItMeans":"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.","caveats":["Discovery cohort of modest size; classes were defined retrospectively.","Spatial patterns need standardised digital pathology to be used clinically."],"changedPractice":false},"route":"/key-papers/paper-gruosso-tnbc-spatial-immune-microenvironments-jci-2019/","neighbours":{"cancer":[{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"digital-pathology-ai","kind":"technology","name":"Digital pathology & AI","route":"/technologies/digital-pathology-ai/"}],"target":[{"id":"b7h4","kind":"target","name":"B7-H4 (VTCN1)","route":"/targets/b7h4/"},{"id":"ido1","kind":"target","name":"IDO1","route":"/targets/ido1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"pathway":[{"id":"immune-desert-exclusion","kind":"pathway","name":"Cold tumours: immune deserts and exclusion","route":"/pathways/immune-desert-exclusion/"},{"id":"tumor-microenvironment","kind":"pathway","name":"Tumour microenvironment (TME)","route":"/pathways/tumor-microenvironment/"}],"term":[{"id":"tils","kind":"term","name":"Tumour-infiltrating lymphocytes (TILs)","route":"/terms/tils/"}],"journal":[{"id":"jci","kind":"journal","name":"Journal of Clinical Investigation","route":"/journals/jci/"}]}}