Single Cell and Spatial Transcriptomics Highlight the Interaction of Club-like Cells with Immunosuppressive Myeloid Cells in Prostate Cancer

According to a newly published study, a specialized epithelial subtype may hold the key to overcoming resistance to prostate cancer treatments. A team of scientists has made a discovery that could explain why certain prostate cancer therapies are less effective than expected. Prostate cancer is still one of the main causes of cancer-related deaths in the World and a major clinical objective is to prevent the spread of cancer and recurrence.

Employing advanced technologies that maintain cells in their native spatial context, the researchers could observe intricate cellular interactions within the tumor microenvironment. This analysis involved 120 patients, identifying a distinct kind of epithelial cells, referred to as club-like cells, which are often found in regions of the tumor characterized by heightened immunosuppressive activity.

Immunosuppression hampers the immune system's ability to eradicate cancer cells. Club-like cells may release substances that attract myeloid-derived suppressor cells to the tumor site and cause such immunosuppression. This not only causes a barrier to existing treatments but may also promote the spread of the disease.

This pivotal study involved collaboration with international partners from the Oslo University Hospital (Insitute for Cancer Research), The Prostate Cancer Research Center (Tampere University in Finland), the Norwegian University of Science and Technology (Trondheim), University College London, and KU Leuven. Directed by Dr. Alfonso Urbanucci (working both in Oslo and Tampere), Professor Matti Nykter, and lead author Antti Kiviaho of the Faculty of Medicine and Health Technology at Tampere University, the research received support from several notable organizations, including the Research Council of Finland, Cancer Foundation Finland, and the Norwegian Cancer Society (Kreftforeningen).

Main Scientific Points of the Study:

1. Role of Club-like Cells in Prostate Cancer: The study identifies club-like cells as a key epithelial cell subtype in the prostate tumor microenvironment (TME).

These cells act as an interface between the prostate and the immune system, displaying a senescence-associated secretory phenotype and being linked to increased polymorpho-nuclear myeloid-derived suppressor cell (PMN-MDSC) activity.
Their presence is associated with myeloid inflammation and resistance to androgen deprivation therapy (ADT).

2. Spatial and Single-cell Transcriptomics: The research employs single-cell RNA-sequencing and spatial transcriptomics to create a comprehensive transcriptomic landscape of the prostate TME from 120 patient samples.

This approach helps in understanding the cellular composition and interactions within the TME, highlighting the heterogeneity and complexity of prostate cancer.

3. Impact of Androgen Deprivation Therapy (ADT): The study investigates the effects of ADT on gene expression in different epithelial cell regions.

It finds that ADT promotes basal and club-like epithelial phenotypes, with decreased expression of androgen receptor-regulated genes in the Tumor and Luminal regions post-treatment.

4. Immunosuppressive Environment: The presence of club-like cells is strongly associated with PMN-MDSC infiltration and immunosuppressive activity in the prostate TME.

This suggests that club-like cells contribute to the immunosuppressive environment, which may play a role in treatment resistance and cancer progression.

Written by: Alfonso Urbanucci, PhD

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland.
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

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