Stromal cell diversity associated with immune evasion in human triple‐negative breast cancer
Autor: | Davendra Segara, Andrew Parker, Alistair R. R. Forrest, Chuan En Lam, Elgene Lim, Chenfei Wang, Joseph E. Powell, James R. Torpy, Kendelle J. Murphy, Daniel L. Roden, Mun N. Hui, Nenad Bartonicek, Holly Holliday, Laurence Gluch, Caroline Cooper, Sunny Z. Wu, Ghamdan Al-Eryani, Alexander Swarbrick, X. Shirley Liu, Paul Timpson, Rui Hou, Jane Beith, Sanjay Warrier, Aurélie Cazet, Elizabeth Robbins, Simon Junankar, Sandra A O'Toole, Thomas R. Cox, Kate Harvey, Brooke A. Pereira, Cindy Mak, Chia Ling Chan |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Resource
Cell signaling Stromal cell Triple Negative Breast Neoplasms Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Extracellular matrix 03 medical and health sciences 0302 clinical medicine medicine Humans Cytotoxic T cell News & Views RNA-Seq Molecular Biology Triple-negative breast cancer 030304 developmental biology 0303 health sciences General Immunology and Microbiology General Neuroscience Phenotype Extracellular Matrix Cancer research Female Tumor Escape Stromal Cells Carcinogenesis Myofibroblast 030217 neurology & neurosurgery T-Lymphocytes Cytotoxic |
Zdroj: | EMBO J |
Popis: | The tumour stroma regulates nearly all stages of carcinogenesis. Stromal heterogeneity in human triple-negative breast cancers (TNBCs) remains poorly understood, limiting the development of stromal-targeted therapies. Single-cell RNA sequencing of five TNBCs revealed two cancer-associated fibroblast (CAF) and two perivascular-like (PVL) subpopulations. CAFs clustered into two states: the first with features of myofibroblasts and the second characterised by high expression of growth factors and immunomodulatory molecules. PVL cells clustered into two states consistent with a differentiated and immature phenotype. We showed that these stromal states have distinct morphologies, spatial relationships and functional properties in regulating the extracellular matrix. Using cell signalling predictions, we provide evidence that stromal-immune crosstalk acts via a diverse array of immunoregulatory molecules. Importantly, the investigation of gene signatures from inflammatory-CAFs and differentiated-PVL cells in independent TNBC patient cohorts revealed strong associations with cytotoxic T-cell dysfunction and exclusion, respectively. Such insights present promising candidates to further investigate for new therapeutic strategies in the treatment of TNBCs. |
Databáze: | OpenAIRE |
Externí odkaz: |