image: On the left is a tissue sample from the prostate stained with hematoxylin and eosin. Hematoxylin stains the nuclei blue or purple because it binds to DNA, and eosin stains the cytoplasm and proteins red or pink. This method is used in the diagnosis of prostate cancer. Visium technology (in the centre) allows for spatial genetic information to be obtained, enabling the precise study of RNA expression patterns in different areas of the tissue sample. The dots in the image are data points from which gene expression was measured. The main results of the study were obtained using this technology. On the right is a mIHC (multiplex immunohistochemistry) microscope image showing proteins stained with antibodies. This method was used for validation in the study.
Credit: Antti Kiviaho, Tampere University
A recent study reveals that immunosuppression, or reduced immune response, in prostate cancer is associated with a specialised epithelial subtype.
The study, led by researchers at Tampere University, analysed data from 120 prostate cancer patients and identified a novel interaction between the immune system and club-like epithelial cells. Although these cells share a similar origin with cancer cells, they employ a different signalling strategy and are found in areas of tissue with increased immunosuppressive activity.
Immunosuppression is a mechanism that prevents the body’s own defence system from destroying malignant cells, causing a subdued treatment response. Specifically, immunosuppression is elicited by myeloid-derived suppressor cells that infiltrate the tumour microenvironment.
“Myeloid cells are a vital component of a normally functioning immune response. In cancer, the regular function of these cells is disturbed, causing a chronic inflammation and myeloid cell accumulation in the tumour,” says Antti Kiviaho, the first author of the study.
The accumulation of myeloid cells in the tumour is associated with a poor prognosis in patients with advanced, treatment-resistant prostate cancer. Treatment resistance is a major challenge in prostate cancer management, and discovering new strategies to address this issue would lead to more effective tools for combating the disease.
Previous research has shown that blocking myeloid infiltration can re-sensitise tumours to commonly used androgen deprivation therapy, which reduces the levels of male hormones that promote tumour growth. In the study, club-like cells were found to be resistant to androgen deprivation.
“Our study implicates club-like cells in this process, but further investigation into their specific function is necessary,” adds Dr Alfonso Urbanucci.
The study utilised technologies that allowed researchers to observe cells in their original spatial environments. This methodology was key to uncovering cell-cell interactions within the tumour microenvironment.
“Many of the previously used protocols lose the spatial information of cells, making it difficult to understand their organisational patterns in live tissue. The discovery of joint localisation between club-like and myeloid cells would not have been possible without this information,” Professor Matti Nykter comments.
The study was conducted in collaboration with researchers from the Norwegian University of Science and Technology, University College London in the UK, and KU Leuven in Belgium. The study was led by Professor Matti Nykter, Dr Alfonso Urbanucci, and first author Antti Kiviaho from the Faculty of Medicine and Health Technology at Tampere University. It was supported by the Research Council of Finland, Cancer Foundation Finland, and the Norwegian Cancer Society (Kreftforeningen).
Journal
Nature Communications
Article Title
Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid cells in prostate cancer
Article Publication Date
16-Nov-2024