Integration of single-cell RNA and protein data identifies novel clinically-relevant lymphocyte phenotypes in breast cancers
Al-Eryani, G.; Bartonicek, N.; Chan, C.-L.; Anderson, A.; Harvey, K.; Wu, S. Z.; Roden, D.; Wang, T.; Reeves, J.; Yeung, B. Z.; Masle-Farquhar, E.; Goodnow, C. C.; Ma, C.; Phan, T. G.; Lundeberg, J.; Junankar, S.; Swarbrick, A.
Show abstract
Immune cells are critical determinants of solid tumour aetiology, but the diverse phenotypes of intra-tumoural immune cells remain incompletely characterised. We applied integrated single cell RNA sequencing (scRNA-Seq) and highly multiplexed protein epitope analysis to a cohort of breast cancer samples to resolve cell states within the tumour microenvironment. We reveal novel protein markers for resting and activated tumour infiltrating lymphocytes, and show that high expression of CD103 primarily marks exhausted CD8 rather than tissue resident CD8 T-cells in human breast cancers. We identify two distinct states of activated CD4+ T follicular helper (Tfh) cells. A population resembling conventional Tfh (cTfh) cells were localised primarily to lymphoid aggregates by spatial transcriptomics. In contrast, cancer associated Tfh (caTfh) cells expressing markers of tissue residency and exhaustion co-localized with cancer foci and signalled to macrophages. Importantly, increased caTfh : cTfh ratio associated with improved disease outcome and response to checkpoint immunotherapy.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Mapping the tumor stress network reveals dynamic shifts in the stromal oxidative stress response 96%
- Stromal remodeling regulates dendritic cell abundance and activity in the tumor microenvironment 95%
- CD8+ T Cell Metabolic Rewiring Defined by Single-Cell RNA-Sequencing Identifies a Critical Role of ASNS Expression Dynamics in T Cell Differentiation 95%
Similar papers in this journal
- Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma 96%
- A Modular Master Regulator Landscape Determines the Impact of Genetic Alterations on the Transcriptional Identity of Cancer Cells 95%
- Neoantigen-driven B cell and CD4+ T follicular helper cell collaboration promotes robust anti-tumor CD8+ T cell responses 95%
Similar papers in this journal
- Tissue-resident NK cells support survival in pancreatic cancer through promotion of cDC1-CD8T activity 95%
- Spatially defined multicellular functional units in colorectal cancer revealed from single cell and spatial transcriptomics 95%
- T cell receptor convergence is an indicator of antigen-specific T cell response in cancer immunotherapies 95%
Similar papers in this journal
- Spatial analysis of human lung cancer reveals organized immune hubs enriched for stem-like CD8 T cells and associated with immunotherapy response 95%
- Sodium chloride in the tumor microenvironment enhances T-cell metabolic fitness and cytotoxicity 95%
- Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program 95%
Similar papers in this journal
- Spatiotemporal co-dependency between macrophages and exhausted CD8+ T cells in cancer 97%
- High-resolution single-cell atlas reveals diversity and plasticity of tissue-resident neutrophils in non-small cell lung cancer 96%
- Lymphocyte networks are dynamic cellular communities in the immunoregulatory landscape of lung adenocarcinoma 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.