The Effects of Hyperthermic Intraperitoneal Chemotherapy on the Peritoneal Microenvironment of High-Grade Serous Ovarian Cancer
Loading...
Embargo End Date
2027-01-01
ICR Authors
Authors
Karim, F
Document Type
Thesis or Dissertation
Date
2025-12-17
Date Accepted
Abstract
Hyperthermic intraperitoneal chemotherapy (HIPEC) given at the time of interval cytoreductive surgery for high-grade serous ovarian
cancer (HGSOC) improves patient survival. The mechanism underlying this eBect has not been determined. Previous work has shown that
systemic chemotherapy alters the tumour microenvironment of HGSOC. To date, the eBect of HIPEC on the peritoneal microenvironment
has not been studied.
In this thesis, I assessed the eBects of HIPEC on the peritoneal microenvironment of HGSOC using human peritoneal samples obtained
pre and post HIPEC at the time of interval cytoreductive surgery.
I investigated immune cell population levels, intercellular distances and localisation to the peritoneal surface using
immunohistochemistry and multiplex imaging with the Cell DIVE platform. I used real-time tissue imaging and Imaris analysis to assess
the immune cell movement within the peritoneum pre and post HIPEC. Furthermore, I evaluated the changes in the extracellular matrix
with Masson’s Trichome staining and TWOMBLI analysis, and cytokine alterations using Meso Scale Discovery assays following HIPEC.
I found no change in immune cell levels following HIPEC, but Cell DIVE analysis showed that immune cells moved closer to the peritoneal
surface, with reduced intercellular distances, after HIPEC. This change in tissue localisation was particularly noticeable for CD68+
macrophages and CD8+ T cells. Real-time imaging analysis demonstrated that CD14+ macrophages and CD8+ T cells moved significantly
faster, further and straighter post HIPEC. There was no change in collagen architecture, collagen percentage or fibronectin percentage
after HIPEC. HIPEC, however, significantly upregulated predominantly pro-inflammatory cytokines.
I conclude that the alterations in immune cell location and movement after HIPEC may be explained by the modulation of cytokine
networks in the peritoneal tissue.
Citation
2025
DOI
Source Title
Publisher
Institute of Cancer Research (University Of London)
ISSN
eISSN
Collections
Research Team
iProgress User