Microenvironment profiling of high-grade serous ovarian cancer

Abstract

Ovarian cancer is among the most lethal gynecological malignancies, with high-grade serous ovarian cancer (HGSOC) being the most aggressive and prevalent subtype. This heterogeneous disease is typically diagnosed at an advanced stage and is associated with high relapse rates. Increasing attention is being directed toward the tumor microenvironment (TME), a complex and dynamic network of non-cancerous cells and extracellular components that may play a critical role in influencing tumor progression and therapeutic response. Given the limited knowledge available on the TME of HGSOC, this study aimed to assess the presence of specific immune and stromal components and their potential relevance to patient outcomes.
In this study, tissue from both primary and metastatic tumor samples were analyzed. Tissue microarrays were stained with biomarkers and imaged via immunofluorescent microscopy. Subsequently, the distribution of immune and stromal components and their association with progression-free survival was assessed.
Compared to primary tumors, metastases showed significantly more heterogeneous tumor microenvironment, with increased presence of CD8+ cytotoxic T cells, FoxP3+ regulatory T cells and elevated α-smooth muscle actin (α-SMA) levels. These results were consistent with the observed intra-patient variability, indicating a shift in the tumor microenvironment composition during tumor metastasis. Kaplan-Meier survival analysis identified α-SMA as a marker of poor survival in the full cohort and in primary tumors. Additionally, the ratio of CD163+ M2-like macrophages was associated with reduced progression-free survival in metastatic tumors, suggesting a context-dependent prognostic role.

Popular Abstract

New clues in the fight against ovarian cancer hidden in the tumor’s surroundings Looking beyond the tumor itself, this study shows that nearby immune and support cells may hold the key to patient survival in ovarian cancer. High-grade serous ovarian cancer (HGSOC) is one of the most lethal gynaecological cancers. It is aggressive and incredibly diverse, making it difficult to detect early, challenging to treat and even harder to predict how a patient will response to therapy. So how do we outsmart a cancer that refuses to play by the rules? One promising strategy may lie not in the tumor itself, but in its surroundings. My thesis project focused on the tumor microenvironment (TME), which is the collection of immune cells, connective tissue and other non-cancerous neighbours that surround a tumor. These cells can either support or suppress cancer growth, and by understanding their role we may be able to identify which patients have a better or worse prognosis. To investigate this, we developed a panel of biomarkers, in this case meaning an array of markers present on different types of TME components, which enabled us to map out their presence in the samples. We looked specifically at so called cytotoxic T cells, regulatory T cells and M2-like macrophages, where the first one is involved in cancer cell killing and the other two have tumor-promoting functions. Additionally, we also looked at the tumor cells and smooth muscle actin, which is a protein and we suspected to predict worse clinical outcomes. These biomarkers were visualized using a fluorescent microscope. The images were then processed and cell types in each tissue sample were quantified and analysed in combination with clinical data. We discovered that patients with increased presence of smooth muscle actin was likely to relapse, suggesting that this TME component may play an important role in helping tumors resist treatment. M2-like macrophages were linked with worse clinical outcomes, but only in tumors that has spread. This suggests that as cancer spreads, its surrounding environment changes substantially. However, cytotoxic T cells were associated with better survival, but only when their presence was analysed relative to tumor cell count per sample. This
highlights how much the immune response depends on context, what we saw in the original tumor’s microenvironment was not the same as in the tumors that had spread. These early findings suggest that a detailed look at the TME could help stratify patients, potentially guiding future treatment decisions. To sum it up, the TME in HGSOC is not just background noise, it holds information that could reshape how we understand, predict and eventually treat this complex disease.

• author: Derzsi-Kovács, Szávitri Virág
• supervisor: Anna Sandström Gerdtsson; Asger Meldgaard Frank
• organization: Department of Immunotechnology; Educational programmes, LTH
• course: KIMM01 20251
• year: 2025
• type: H2 - Master's Degree (Two Years)
• subject: Biology and Life Sciences; Technology and Engineering; Medicine and Health Sciences
• keywords: Immunotechnology, Tumor microenvironment, TME, Ovarian cancer, OC, High-grade serous ovarian cancer, HGSOC
• language: English
• id: 9196976
• date added to LUP: 2025-06-11 12:46:18
• date last changed: 2025-06-11 12:46:18