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Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
Published on: March 14, 2014
Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid
Antti Kiviaho1,2, Sini K Eerola1,2, Heini M L Kallio1,2
1Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Abstract:
Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated the mechanisms through which cancer cells escape treatment, but their relation toward the tumor microenvironment (TME) remains elusive. Here we present a comprehensive transcriptomic landscape of the prostate TME at multiple points in the standard treatment timeline employing single-cell RNA-sequencing and spatial transcriptomics data from 120 patients. We identify club-like cells as a key epithelial cell subtype that acts as an interface between the prostate and the immune system. Tissue areas enriched with club-like cells have depleted androgen signaling and upregulated expression of luminal progenitor cell markers. Club-like cells display a senescence-associated secretory phenotype and their presence is linked to increased polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) activity. Our results indicate that club-like cells are associated with myeloid inflammation previously linked to androgen deprivation therapy resistance, providing a rationale for their therapeutic targeting.
Insights
Prostate cancer cells develop treatment resistance partly via interactions with the tumor microenvironment. Researchers identified club-like cells as key players, linking them to inflammation and resistance to androgen deprivation therapy.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Prostate cancer treatment resistance is a major clinical challenge.
- Understanding the tumor microenvironment's (TME) role in resistance is crucial but incomplete.
- Mechanisms of resistance often involve complex interactions between cancer cells and their surrounding TME.
Purpose of the Study:
- To comprehensively map the transcriptomic landscape of the prostate TME during cancer treatment.
- To identify specific cell types and molecular pathways involved in treatment resistance.
- To investigate the relationship between epithelial cell subtypes and immune cell activity in the TME.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) of TME cells from 120 prostate cancer patients.
- Spatial transcriptomics to map cell locations and interactions within the TME.
- Analysis of transcriptomic data at multiple time points during standard treatment.
Main Results:
- Identified club-like cells as a novel epithelial subtype interfacing with the immune system.
- Club-like cells exhibit depleted androgen signaling and upregulated luminal progenitor markers.
- These cells show a senescence-associated secretory phenotype and correlate with increased polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) activity.
- Enrichment of club-like cells is associated with myeloid inflammation linked to androgen deprivation therapy resistance.
Conclusions:
- Club-like cells are a critical component of the prostate TME associated with treatment resistance.
- These cells may mediate resistance through interactions with myeloid-derived suppressor cells and inflammation.
- Targeting club-like cells presents a potential therapeutic strategy to overcome prostate cancer treatment resistance.
