Ovarian cancer is said to be the most intractable disease of gynecologic cancer.
In recent years, a mechanism called "cancer immune escape" has been elucidated in which cancer cells proliferate while evading the attack of immune cells by various methods.A research group at Kyoto University has been conducting research on immune escape from ovarian cancer for many years, and has announced that it has clarified a new mechanism for cancer immune escape.
In this study, ovarian cancer has a particularly poor prognosis when a group of genes related to the cell morphological change process called epithelial mesenchymal transition is expressed at a high level, so Snail is one of the gene clusters. Focus on.We found that reducing Snail expression in a mouse ovarian cancer model slowed cancer growth.
Next, from gene expression analysis of cell lines with reduced Snail expression, it was discovered that the expression of chemokines such as CXCL1 and CXCL2 was also reduced.From molecular chemistry studies, we found that Snail induces the expression of CXCL1 and CXCL2.It has been reported that these chemokines induce the migration of myeloid-derived immunosuppressive cells (MDSC) by acting on a receptor called CXCR2, and MDSC has the effect of suppressing the immune attack against ovarian cancer.
From the above, it was shown that ovarian cancer secretes CXCL1 and CXCL2 through the expression of Snail and induces MDSL into the tumor via CXCR2 to suppress antitumor immunity.Furthermore, based on this result, when a CXCR2 inhibitor was administered to ovarian cancer model mice, the number of MDSCs entering the tumor decreased, and the growth of the tumor was suppressed, resulting in a therapeutic effect. , CXCR inhibitors have been suggested to be promising for new immunotherapies.
This result is an important result that elucidates the mechanism of immune escape of ovarian cancer and leads to the development of new therapies, and its future clinical application is strongly expected.
Paper information:[Nature Communications] Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation
