Single cell

A Single-cell Map of Intratumoral Changes during Anti-PD1 Treatment of Patients with Breast Cancer

 

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  • Immune-checkpoint blockade (ICB) combined with neoadjuvant chemotherapy improves pathological complete response in breast cancer. To understand why only a subset of tumors respond to ICB, patients with hormone receptor-positive or triple-negative breast cancer were treated with anti-PD1 before surgery. Paired pre- versus on-treatment biopsies from treatment-naive patients receiving anti-PD1 (n = 29) or patients receiving neoadjuvant chemotherapy before anti-PD1 (n = 11) were subjected to single-cell transcriptome, T cell receptor and proteome profiling. One-third of tumors contained PD1-expressing T cells, which clonally expanded upon anti-PD1 treatment, irrespective of tumor subtype. Expansion mainly involved CD8+ T cells with pronounced expression of cytotoxic-activity (PRF1GZMB), immune-cell homing (CXCL13) and exhaustion markers (HAVCR2LAG3), and CD4+ T cells characterized by expression of T-helper-1 (IFNG) and follicular-helper (BCL6CXCR5) markers. In pre-treatment biopsies, the relative frequency of immunoregulatory dendritic cells (PD-L1+), specific macrophage phenotypes (CCR2+ or MMP9+) and cancer cells exhibiting major histocompatibility complex class I/II expression correlated positively with T cell expansion. Conversely, undifferentiated pre-effector/memory T cells (TCF7+GZMK+) or inhibitory macrophages (CX3CR1+C3+) were inversely correlated with T cell expansion. Collectively, our data identify various immunophenotypes and associated gene sets that are positively or negatively correlated with T cell expansion following anti-PD1 treatment. We shed light on the heterogeneity in treatment response to anti-PD1 in breast cancer.
  • A single-cell map of intratumoral changes during anti-PD1 treatment of patients with breast cancer - Bassez et al. – 2021 – NATURE MEDICINE

 

Data availability

Raw sequencing reads of all single-cell experiments (scRNA-seq, scTCR-seq and CITE-seq) have been deposited in the European Genome-phenome Archive (EGA) under study no. EGAS00001004809 (with a summary of the BioKey study and patient characteristics) and with data accession no. EGAD00001006608 (to access the data). Requests for accessing raw sequencing reads will have to be reviewed by the UZLeuven-VIB data access committee. Any data shared will only be released prior to a Data Transfer Agreement that will have to include the necessary conditions to guarantee protection of personal data (according to European GDPR law). 

Alternatively, a download of the read count data is more readily available from this website. In addition to the read counts, the following meta-data have been added to the files: i) patient number (to allow pairing of pre- and on-treatment samples to an individual patient level), ii) type of sample (pre- versus on-treatment), iii) treatment (anti-PD1 monotherapy versus prior chemotherapy plus anti-PD1), iv) expansion status (expander versus non-expander) and v) hormone receptor status (e.g., triple negative, estrogen receptor-positive, etc). Please note that patient numbers have been randomized not to match those highlighted in Supplementary Table 1 from Bassez et al. (Nature Medicine 2021).

Additionally,  a datafile containing scTCR-data can be downloaded. This contains CellRanger output clonotype files that are combined for all samples. The same sample labels as used for the read count matrix are used to be distinguish clonotypes from different samples. Barcode information (cell IDs) for these clonotypes is also given in a combined file, to allow clonotype information to be linked with counts and metadata files.

Data files