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BIOKEY: A single-cell catalogue of the dynamic changes underlying Checkpoint Immunotherapy response in Early Breast Cancer

Checkpoint immunotherapy combined with neoadjuvant chemotherapy improves complete pathologic response in a subset of breast cancer patients. Here, we applied single-cell profiling to tumor biopsies collected before and during anti-PD1 therapy. One-third of tumors exhibited proliferative T-cells expanding along CD8+ or CD4+ lineages, which were either characterized by increased cytotoxicity and exhaustion or improved T-helper function, respectively. Lineage tracing in non-expanding tumors revealed at which point in the lineage T-cells were impaired, while gene expression modeling along these lineages revealed novel genes and underlying transcription factors involved in T-cell expansion. Interestingly, different dendritic and myeloid cell phenotypes could either stimulate or inhibit expanding T-cells, while cell-to-cell communication revealed an integrated immune context highly predictive of T-cell expansion, consisting of immune-stimulatory/-inhibitory interactions between cancer and various immune cell types. Our data yield unprecedented insights into the dynamic changes underlying checkpoint immunotherapy response in breast cancer.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001006608 Illumina NovaSeq 6000 84
EGAD00001007056 Illumina HiSeq 4000 29
EGAD00001007057 Illumina HiSeq 4000 30
EGAD00001007058 Illumina HiSeq 4000 Illumina NovaSeq 6000 16
Publications Citations
CIDER: an interpretable meta-clustering framework for single-cell RNA-seq data integration and evaluation.
Genome Biol 22: 2021 337
7
Bulk and Single-Cell Profiling of Breast Tumors Identifies TREM-1 as a Dominant Immune Suppressive Marker Associated With Poor Outcomes.
Front Oncol 11: 2021 734959
6
Neoantigen-specific CD4<sup>+</sup> T cells in human melanoma have diverse differentiation states and correlate with CD8<sup>+</sup> T cell, macrophage, and B cell function.
Cancer Cell 40: 2022 393-409.e9
33
Integrated Analysis of Single-Cell and Bulk RNA-Sequencing Reveals a Tissue-Resident Macrophage-Related Signature for Predicting Immunotherapy Response in Breast Cancer Patients.
Cancers (Basel) 14: 2022 5506
1
Orthogonal cytokine engineering enables novel synthetic effector states escaping canonical exhaustion in tumor-rejecting CD8<sup>+</sup> T cells.
Nat Immunol 24: 2023 869-883
7