Poster Presentation 38th Lorne Cancer Conference 2026

Dissecting the tumour-neural microenvironment in prostate cancer (#246)

Lauren Ryan 1 2 3 , Melissa Thomas 1 3 , Birunthi Niranjan 4 , Shivakumar Keerthikumar 4 , Eva Apostolov 2 3 , Min Huang 2 5 , Alex Swarbrick 2 3 , Andrew Ryan 6 , Mitchell Lawrence 4 7 8 , Susan Clark 1 2 3 , Ruth Pidsley 1 2 3
  1. Cancer Epigenetics Laboratory, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. St. Vincent’s Clinical School, UNSW Sydney, Darlinghurst, NSW, Australia
  3. Cancer Ecosystem Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  4. Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
  5. SydPath Department of Anatomical Pathology, St Vincent’s Hospital, Sydney, NSW, Australia
  6. TissuPath Specialist Pathology Services, TissuPath, Mount Waverley, VIC, Australia
  7. Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  8. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia

Background: Prostate cancer is a leading malignancy among men globally. The 5-year survival rate for patients with localised prostate cancer is 99%, but only 36% for patients with distant metastasis. Perineural invasion (PNI) refers to the movement of tumour cells along or within nerve bundles. The detection of PNI in diagnostic prostate biopsies is associated with an increased risk of bone metastases and lethal disease [1].

Prostate tumour cells exist in a complex tumour microenvironment (TME) which includes non-malignant cancer associated fibroblasts (CAFs). CAFs have been shown to regulate the phenotype of prostate epithelial cells to promote tumorgenicity, as well as altering the TME architecture to form supportive niches for cancer cell proliferation. However, in the development of prostate cancer there is limited understanding of the role of CAFs in the neural niche, and their potential role in promoting nerve growth and facilitating PNI; features associated with aggressive disease.

Methods:  We performed an integrative transcriptomic analysis on a large cohort of patient-matched CAF and normal prostate fibroblasts (NPFs) from radical prostatectomy (RP) samples. This included bulk RNA-sequencing (n=62 pairs), scRNA-sequencing (n=5 pairs) and Xenium spatial sequencing on RP tissue (n=5 patient-matched tumour and benign regions, n=2 additional tumours). We performed differential gene expression analyses and unsupervised clustering of single-cell data to identify CAF and NPF subtypes and integration with Xenium data to interrogate their functional significance.

Results: By leveraging bulk, single-cell and spatial transcriptomic approaches we have characterised differences in expression profiles between CAFs and NPFs. Importantly we identified a novel CAF subtype that localises to nerves, termed perineural CAFs (pnCAFs). Through investigation of pnCAFs in their tissue context we observe a tumour specific, PNI region signature. Our results suggest that pnCAFs play a key role in the neural-tumour microenvironment, through cell-cell signalling and matrix remodelling.

Conclusion: Using high-resolution spatial transcriptomics, we have identified a pnCAF subtype with a strong spatial localisation to PNI nerves. Our data provide new insights into the potential role of CAFs in remodelling nerves for the promotion of localised/metastatic prostate cancer disease, with further biological validation to be performed.

  1. 1. Ciftci, S., et al., Perineural invasion in prostate biopsy specimens is associated with increased bone metastasis in prostate cancer. Prostate, 2015. 75(15): p. 1783-9.