Association of ovarian tumor epithelium coexpressing HLA-DR and CA-125 antigens with tumor infiltrating cytotoxic T lymphocytes

Abstract

Understanding of the relationship between tumor infiltrating cytotoxic T lymphocytes (CD 8+TILs) and tumor cells as well as tumor-associated antigens is important and may reflect the extent of immune response of the patient to the tumor, thus providing a useful clue relevant to the prognosis. The purpose of this study was to determine the relationship between the expression of HLA-DR and CA-125 antigens and the presence of CD 8+TILs with regard to the established clinicopathological factors of ovarian carcinomas using immunohistochemical methods. Thirty-one ovarian carcinomas consisting of 20 serous, 7 mucinous, and 4 clear cell types were examined. Of these, 18 (58%) and 22 (71%) were positive for HLA-DR and CA-125 antigens respectively, and the overall mean number of the CD 8+TILs was 7.2±2.9. A significant association was observed between the mean number of CD 8+TILs and tumor grade (P = 0.01), disease stage (P = 0.003), and patient outcome (P = 0.01) . The mean number of CD8+TILs in HLA-DR positive (8.6±2.2) or CA-125 positive (8.4±2.1) tumors was significantly higher than that in HLA-DR negative (5.2±2.5;P = 0.0003) or CA-125 negative (4.2±2.2;P = 0.00002) tumors. These signifcant levels were further enhanced by one order of magnitude when the mean number of CD 8+TILs in tumors postive for both HLA-DR and CA-125 antigens (9.1±1.7) was compared to that in HLA-DR negative or CA-125 negative tumors. The frequency of cancer-related deaths in HLA-DR and CA-125 positive tumors was significantly lower than in the negative tumors (P =0.01). These data suggest that concurrent expression of HLA-DR and CA-125 antigens may augment the immune response of the patient to the tumor, thus providing a potential clue relevant to the prognosis.