Can single-cell RNA sequencing identify mechanisms of response to neoadjuvant therapy in breast cancer?

For her research presented at ESMO 2024, Dr Marcela Carausu, medical oncologist at the Institut Jules Bordet in Brussels, uses single-cell RNA sequencing (scRNA-seq) to provide insights into cellular and molecular characteristics that can predict a response or resistance to neoadjuvant therapy (NAT) in patients with high-risk early-stage breast cancer. In this video, Dr Carausu shares the key take-aways from these investigations with Dr Elisa Agostinetto (Institut Jules Bordet, Brussels, Belgium).

Tissue samples were prospectively collected from pre-treatment tumor biopsies, post-treatment tumor beds, and normal adjacent tissue of early-stage breast cancer patients who were treated with standard-of-care NAT between 2021-2023. In total, high-quality scRNA-seq data were obtained for 65 samples from 30 patients (18 responders). These scRNA-seq data helped to differentiate lymphocytic subpopulations that are specific for tumors, which illustrates at a more granular level how tumours reshape their microenvironment. CD8+ CXCL13+ T-cells are terminally differentiated T-cells that arise after an effective tumour-reactive immune response. Interestingly, the expansion of these cells at baseline proved to be associated with a response to NAT. A possible explanation for this association is that these CD8+ CXCL13+ T-cells have specific interactions with T follicular helper cells and B-cells. These interactions subsequently induce certain tertiary lymphoid structures that allow a better anti-tumour immune response, ultimately leading to a better response to neoadjuvant chemo-immunotherapy.