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ONCOLOGY, NUCLEAR MEDICINE AND TRANSPLANTOLOGY

Keyword: Tumour Microenvironment

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Review Article
Tumor–Immune Interactions in Prostate Cancer: Insights from Single-Cell and Spatial Genomics
Oncology, Nuclear Medicine and Transplantology, 2(2), 2026, onmt020, https://doi.org/10.63946/onmt/18860
ABSTRACT: Prostate cancer still remains one of the most common cancers in men worldwide, and it is a great therapeutic challenge, especially in the field of immunotherapeutics. The tumour microenvironment (TME) is immunologically “cold” in prostate cancer, and influenced by intrinsic molecular characteristics of the disease such as androgen receptor (AR) signalling, PTEN loss, and lineage plasticity towards neuroendocrine prostate cancer (NEPC). Together, these aspects inhibit antigen presentation, block the entry of cytotoxic T cells and help to establish spatially organised immunosuppressive niches, providing a rational explanation for the clinical variability and partial efficacy of immune-based therapies.
Traditional bulk genomic approaches have provided important insights into tumour biology but are unable to capture the cellular and spatial complexity of tumour–immune interactions. These developments have been spurred by recent advancements in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics, which allow to detect individual cell subpopulations within intact tumour tissues, such as exhausted T cells co-expressing PD-1, TIM-3, LAG-3 and TIGIT, immunosuppressive SPP1+ macrophages and various cancer-associated fibroblast subpopulations. These technologies have identified specific immune exclusion sites, stromal–epithelial immune silencing barriers, and therapeutic resistance and immune evasion regulatory programs in the context of prostate cancer specifically.
However, there are still many technical challenges that need to be overcome, such as the lack of patient samples and their demographic diversity, data integration, lack of spatial characterisation of bone metastases and difficulties in clinical translation. Comprehensive multi-omics atlases, AI-driven spatial pattern recognition, functional validation of potential targets and prospective clinical trials based on biomarkers are all important areas for future research. They show significant potential for the creation of better, personalized immunotherapeutic treatment for prostate cancer.