Suggesting the possibility of customized treatment for ovarian cancer patients without gene mutation
Aug 11, 2024
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Ovarian cancer is a female cancer with the highest mortality rate in Korea. Globally, it has a 5-year survival rate of less than 40%, and most patients experience recurrence within 2 years of diagnosis. Repeated recurrence leads to resistance to treatment, so prevention of recurrence is a major challenge in ovarian cancer treatment.
Recently, targeted chemotherapy using a 'polymerase (PARP) inhibitor' has been contributing to the improvement of survival in patients with 'BRCA 1/2 gene mutation', one of the major causes of ovarian cancer. However, targeted chemotherapy that is effective in improving the survival rate of patients without 'BRCA 1/2 gene mutations, which accounts for more than 50% of ovarian cancer patients, has not yet been established, and research on this is being actively conducted worldwide.
In response, a joint research team led by obstetrics and gynecology professors Park Joon-sik and Kim Jeong-cheol at Soonchunhyang University Bucheon Hospital (Lee Jung-yoon, obstetrics and gynecology professor at Yonsei University Severance Hospital, and Park Soo-hyung, professor at KAIST Graduate School of Medicine) conducted a study to compare and analyze the characteristics of tumor immune microenvironment and response to immune anticancer drugs according to the presence of 'BRCA 1/2 gene mutation'.
The joint research team collected tumor tissue and clinical information of 117 newly diagnosed ovarian cancer patients from April 2018 to March 2022 and isolated 'tumor infiltrating lymphocytes', immune cells that attack cancer tissue in tumor microenvironment. We measured and analyzed the immune phenotype of isolated tumor infiltrating lymphocytes and their responsiveness to 'anti-PD-1 immunotherapy' which inhibits immune checkpoint receptor 'PD-1', and identified tumor immune microenvironmental characteristics according to 'BRCA 1/2 gene mutation'.
Results showed that the risk of recurrence in ovarian cancer patients with 'BRCA 1/2 gene mutation' was approximately 70% lower than in ovarian cancer patients without gene mutation, and tumor infiltrating lymphocytes 'CD8 T cells' in ovarian cancer with gene mutation showed severe immune exhaustion characteristics compared to ovarian cancer without gene mutation.
In addition, experiments measured the reactivity of tumor-invasive lymphocytes to the immuno-cancer drug 'PD-1 inhibitor'. Ovarian cancer patients without 'BRCA 1/2 gene mutation' had higher resilience to tumor-invasive lymphocytes 'CD8 T cells' than patients with gene mutations. Furthermore, it was confirmed that among ovarian cancer patients without genetic mutations, 'PD-1 high-profile group' had higher immune cell resilience by 'anti-PD-1 immunotherapy'.
Based on the survival information of 117 ovarian cancer patients who participated in this study, the research team compared the progression-free survival period and found that the risk of recurrence when treated with immuno-cancer drugs was about 60% lower in ovarian cancer patients without 'BRCA 1/2 gene mutation', suggesting the possibility of treating immuno-cancer drugs 'PD-1 inhibitor' in ovarian cancer patients without 'BRCA 1/2 gene mutation'.
Professor Park Jun-sik confirmed that the effect of immuno-oncology on the function of lymphocytes in tumors varies depending on whether there is a 'BRCA1/2 gene mutation' through this study. "Selecting patients with high tumor infiltrating CD8 T lymphocytes with high expression of 'PD-1' among patients without 'BRCA1/2 gene mutations' would allow the immuno-oncology drug 'PD-1 inhibitor' to be an effective therapeutic strategy."
"Further research will be conducted to establish customized treatment strategies for ovarian cancer patients under various conditions to improve survival rates in ovarian cancer patients in the future."
On the other hand, the results of this study were published in the recent issue of JITC (Journal for ImmunoTherapy of Cancer, IF: 10.3) under the title of 'Unique Immune Characteristics and Differential Anti-PD-1-mediated rehabilitation potential of CD8+ TILs based on BRCA1/2 mutation status in clinical ovarian dancers'
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