Scientific Session
AB078. SOH25_AB_135. Extracellular vesicles in colorectal cancer: drivers of CMS4 tumour-induced immune modulation and potential biomarkers
Anastasija Walsh1, Lei Lei1, Norashikin Zakaria1, Sean Hynes2, Margaret Sheehan3, Aoife Canney3, Aisling Hogan4, Roisin Dwyer5, Aideen Ryan1
1Division of Anatomical Pathology, University of Galway, Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Science, Galway, Ireland;
2University of Galway, Discipline of Pathology, School of Medicine, College of Medicine, Nursing and Health Sciences, Clinical Science Institute, Galway, Ireland;
3Division of Anatomical Pathology, Galway University Hospital, Galway, Ireland;
4Department of Colorectal Surgery, Galway University Hospital, Galway, Ireland;
5University of Galway, Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Science, Galway, Ireland
Background: CMS4 colorectal cancer (CRC), one of four consensus molecular subtypes of CRC, is characterised by an immuno-suppressive tumour microenvironment. Its characteristics include presence of cancer-associated fibroblasts (CAFs) and elevated transforming growth factor-beta (TGF-β) production, which contribute to resistance against immune-based therapies. Extracellular vesicles (EVs) are essential mediators of communication within the tumour microenvironment. Cancer-derived EVs often contain immunomodulatory ligands. This study aims to investigate the immunomodulatory ligands on patient plasma EVs and examine how primary human CAF EVs influence immune cells and stroma within the tumour.
Methods: CAFs and matched normal-associated fibroblasts (NAFs) were isolated from tumour and adjacent non-cancerous tissue, respectively. Patient blood was collected and plasma isolated. Informed consent was obtained prior to sampling. Cell secretome was generated from outgrown CAFs/NAFs. CAF/NAF derived EVs were depleted from secretome. Immunomodulatory effects of complete or EV depleted secretome on natural killer (NK) cells were assessed by analysing immunosuppressive/activation markers. EVs were isolated from CRC patient and health plasma and expression of immunomodulatory markers compared.
Results: Plasma from CRC patients contained significantly higher EV concentrations than healthy plasma. Immunomodulatory markers such as PD-L1 and CD24 were present on EVs, with slightly elevated expression in CRC patients. CAF secretome significantly impacts expression of NK cell immunomodulatory markers; however, EV removal abrogates these effects, suggesting an EV-mediated effect.
Conclusions: Plasma-derived EVs carry immunosuppressive proteins commonly associated with tumours, highlighting their potential as biomarkers. Removing EVs from cancer or CAF secretome reduces their immunosuppressive effects. This emphasizes EVs as critical regulators of immune modulation within the tumour microenvironment, highlighting potential therapeutic targets to counteract cancer immune evasion.
Keywords: Colorectal cancer (CRC); extracellular vesicles (EVs); cancer-associated fibroblasts (CAFs); natural killer cells (NK cells); immunomodulation
Acknowledgments
None.
Funding: None.
Conflicts of Interest: The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
doi: 10.21037/map-25-ab078
Cite this abstract as: Walsh A, Lei L, Zakaria N, Hynes S, Sheehan M, Canney A, Hogan A, Dwyer R, Ryan A. AB078. SOH25_AB_135. Extracellular vesicles in colorectal cancer: drivers of CMS4 tumour-induced immune modulation and potential biomarkers. Mesentery Peritoneum 2025;9:AB078.
