[ABSTRACT] Single-cell mRNA expression of PBMCs reveal dynamic immunomodulatory features of metastatic breast cancer
| Main Author: | Stefano Mangiola |
|---|---|
| Format: | Article Journal |
| Terbitan: |
, 2021
|
| Online Access: |
https://zenodo.org/record/5750992 |
Daftar Isi:
- Several single-cell studies have reported transcriptomic, genomic and epigenomic dysregulation in breast cancer. However, the peripheral immune landscape of breast cancer remains poorly understood. We report an integrated analysis of the single-cell transcriptomes of more than 65,000 peripheral blood mononuclear cells (PBMCs) of stable oligometastatic and progressive metastatic breast cancer patients. Deconvolution of PBMCs revealed major myeloid and lymphoid immune cells, including rare T cell lineages of MAIT and Gamma delta T cells, thus revealing previously unreported immune subsets in metastatic breast cancer. Regardless of the extent of the metastatic burden, the cancer patients profile indicates global enrichment of proinflammatory NKG7 high monocytes, M1 macrophages, migratory myeloid, T memory stem cells (TSCM), CD4 T effector memory (TEM) and CD4 T central memory (TCM) cells. Interrogation with healthy donor’s PBMCs single-cell transcriptome shows marked depletion of memory B cells (BMEM), transitional CD8, CD4 central memory (TCM) and MAIT cells in the circulating immune landscape of metastatic breast cancer patients. This suggests that peripheral immune cells can provide a surrogate marker for undiagnosed metastasis. Comparative analysis of stable versus progressive metastatic disease states shows distinct compositional and gene expression changes in PBMCs. The antigen inexperienced CD4 naïve and cytotoxic MAIT cells are relatively depleted in progressive metastatic disease. While the pro-inflammatory classical monocytes and CD4 T effector memory (TEM) cell levels are elevated in stable metastasis, they diminish in the progressive metastatic state. The receptor-ligand relationship analysis between the two metastatic cohorts revealed unique cell-cell contact, ECM-receptor interactions, and cytokine profile, thus identifying potential new therapeutic targets for metastatic disease. Overall, our study provides a novel resource on the peripheral immune system operating in metastatic breast cancer.