Investigating STING-directed therapy for ovarian cancer using in-vitro models.

Abstract

Ovarian cancer is one of the most lethal gynecological-related cancers and has a
high recurrence rate. Its heterogeneity and immunosuppressive landscape pose challenges when assessing treatment options. Novel immunotherapy strategies have potential to overcome its challenges with heterogeneity and immunosuppression but have not been successful yet. Utilizing the cGAS-STING pathway is promising for
immunosuppressive cancers, particularly using STING signaling as a method to prime the immune system. However, suitable models are required to evaluate STING signaling for ovarian cancer, especially considering its multiple histotypes. In this study, two histotypes were selected: low grade serous ovarian cancer (LGSOC) and high grade serous ovarian cancer (HGSOC). Four cell lines were assessed as potential models for STING signaling: HEY and ES2 representing low grade serous ovarian cancer-like models and OVCAR3 (BRCA wildtype) and KURAMOCHI (BRCA2 mutation) representing high grade serous ovarian cancer-like models. Western Blots demonstrate that STING expression is only present in HEY and KURAMOCHI. Furthermore, downstream targets TBK-1 is minimally expressed in all cell lines while IRF-3 shows clear bands. Though inconclusive, these results suggest that the variation in STING expression between cell lines may be attributed to baseline STING expression rather than activation of the cGAS-STING pathway. Variations in expression between the BRCA2 mutated vs wildtype high grade serous ovarian cancer-like model suggest a need for further subtype categorization. The low grade serous and high grade serous ovarian cancer models demonstrate heterogeneity within them and therefore cell line models should be validated based on baseline STING signaling instead of the histotype they reflect.

Popular Abstract

Priming the immune system to treat ovarian cancer

According to the 2022 Global Cancer Burden data, 325,000 new cases of ovarian cancer are diagnosed annually. Unfortunately for many of them, the diagnosis is already too late. Ovarian cancer is rarely caught early and its early warning signs (bloating, fatigue, etc.) are easily dismissed until the cancer has unknowingly progressed.

One reason why ovarian cancer is so difficult to treat is that it does not act like one disease. Between patients, tumors can have different genetic makeups, meaning that they can behave differently with different responses to the same treatment. This study focuses on two of five recognized subtypes within ovarian cancer: high grade serous ovarian cancer (HGSOC) and low grade serous ovarian cancer (LGSOC). Understanding the differences between them allows for better classification and assessments of which treatments might work.

Immunotherapy is a treatment that primes the immune system to recognize and attack cancer cells. Immunotherapy has potential for treating ovarian cancer, but the main challenge is that immune cells in ovarian cancer’s tumour environment are not responsive to immunotherapy treatment. Imagine an attacker that learns exactly how to avoid security guards; this is comparable to how ovarian cancers can “hide” from the immune system. To overcome this, we invoke an “alarm system,” the cGAS-STING pathway. The cGAS-STING pathway is a part of the body’s immune system that detects signs of damage by detecting abnormal DNA. This alarm system detects damaged DNA and sends signals the cGAS-STING pathway to wake up and produce immune signals to the area. A core part of this pathway is STING, a protein which triggers the immune response. To assess STING as a treatment target, reliable models are required to understand how it works. An example of a reliable model are cell line models, where cancer cells are grown in the laboratory. In this study, four cell lines were selected for this project. The objective of these experiments is to understand whether STING-directed immunotherapy can be applied to ovarian cancers and furthermore, to evaluate whether the selected four cell lines are suitable models for it. HEY and ES2 are the LGSOC-like models and OVCAR3 and KURAMOCHI are the HGSOC-like models. We tested the cell lines by treating them with a drug which stimulates STING and observing how this changes the expression of cGAS-STING pathway. The results showed that two of the cell line models, ES2 and OVCAR3, do not express STING at detectable levels, raising the question whether they are suitable models for assessing STING-directed therapies. When looking at other targets in the same signaling pathway, we could barely detect the TBK-1 protein and observed higher levels of IRF-3 protein. Future research should investigate cell lines with a high baseline STING expression to more accurately observe changes in the cGAS-STING pathway; unlike HEY, ES2, and OVCAR3 which have a low baseline STING expression. By selecting better cell line models to evaluate STING directed therapy for ovarian cancer, more accurate assessments for treatments can be made. Ultimately, this study sets the groundwork to investigate which models and methods are appropriate for studying STING treatment.

• author: Sampermans, Isis Elena Maria
• supervisor: Anna Sandström Gerdtsson; Asger Meldgaard Frank
• organization: Department of Immunotechnology; Educational programmes, LTH
• course: KIMM01 20261
• year: 2026
• type: H2 - Master's Degree (Two Years)
• subject: Technology and Engineering
• language: English
• id: 9244518
• date added to LUP: 2026-06-26 13:34:39
• date last changed: 2026-06-26 13:34:39