Worldwide ovarian cancer ranks fourth among disease-related causes of death in women with 240,000 new cases each year. Prognosis varies significantly by stage at diagnosis and histologic type. Clear cell ovarian cancer (CCOC), a specific subtype of ovarian cancer, is an epithelial tumor with an especially poor prognosis in advanced stages, showing resistance to platinum-based chemotherapy and spreading to lymph nodes even after surgery. The pathogenesis of CCOC is not fully understood, especially the role of immune cells.
To address this gap, Qinan Xian and colleagues designed a two-sample bidirectional mendelian randomization (MR) study to examine immunotherapeutic targets and provide fresh perspectives on causes clinical management of CCOC.
The study was published in the Journal of Ovarian Research, and the researchers used genome-wide association study (GWAS) data on 731 categories of immune cells and CCOC from the current literature. They also collected ovarian cancer data from the FinnGen database, which included genetic information on 42,307 European participants: 1,366 patients with CCOC and 40,941 healthy individuals. Immunologic data revealed genetic variants responsible for specific immune features, and ovarian cancer data showed which genetic variants were associated with development of CCOC.
The two datasets were combined by means of MR and analyzed side by side. The researchers assessed whether immune cell characteristics increased the risk for CCOC and then assessed whether having CCOC had an effect on immune cell traits.
The results showed that six immune phenotypes were associated with an increased risk for CCOC: DN (CD4- CD8-) AC, IgD- CD38dim % B cells, CD3- CD39 + resting Treg, CD8dim % T cells, CD25hi – CD45RA- CD4 not Treg % CD4+, and CD19- IgD+ CD38- unsw mem. Two B-cell types were particularly important: IgD – CD38dim %B cell and CD19 on IgD + CD38 unswitched memory cells. Because B cells can sometimes support tumor growth through an anti-inflammatory effect that suppresses cells meant to attack a tumor, the presence of these specific B cells in CCOC suggests they may contribute to the progression of the disease.
When the researchers analyzed the results of reverse MR, they observed that patients with CCOC had reduced levels of CD3, a protein found in CD39+ resting regulatory T (Treg) cells. This was a novel discovery suggesting that cancer cells in CCOC may be actively changing the function of CD39+ resting Treg cells to evade immune response.
This study demonstrated the complex role of immune cells in COCC pathogenesis. It also showed that the connection between immunology and COCC deserves further investigation. Additional studies are needed to determine the precise mechanism for immune cells in the occurrence of CCOC.
