Co-culture of human induced pluripotent stem cells (iPSCs) with human fallopian tube epithelium (FTE) induces Pax8 and CK7 expression: Initial steps in modeling fallopian tube epithelium to study serous carcinogenesis

Abstract

strategies under investigation for several cancers. Although antigenic targets for the immune system exist in the form of tumor-associated antigens, no tumor-specific antigens have been identified for gynecologic cancers. Expression of cancer-testis (CT) antigens in ovarian cancer has been described. CT antigens are attractive targets for cancer immunotherapy due to their restricted expression in testis, germ cells, and tumors. The aim of our study was to evaluate the expression of a panel of 20 CT antigens in gynecologic tumor cell lines and to determine if antigen sharing occurs among different gynecologic cancers. Methods: RNA was isolated from 16 gynecologic cancer cell lines (9 epithelial ovarian cancer, 8 endometrial cancer, 1 cervical cancer, and 1 leiomyosarcoma cell line). Real-time polymerase chain reaction analysis was performed to determine the expression level of 20 CT antigens. Results: Expression of CT antigens was identified in gynecologic cancer cell lines. Among 20 evaluated antigens, 90% (18/20) expressed in ovarian and endometrial cancer cell lines, while only 30% (6/20) expressed in cervical cancer and leiomyosarcoma cell lines. The most frequently expressed CT antigens were SP-17 (93.8% of cell lines), MAGE-A4 (87.5%), OYTES (68.8%), BAGE (62.5%), CT-45 (62.5%), PIWIL2 (56.3%), and GAGE (56.3%). CT45, SP-17, and MAGE-A4 were expressed among all gynecologic cancers. We found that different gynecologic cancers shared the expression of CT antigens, with the mean number of antigens shared among cancer types ranging from 3 to 4.6 antigens. There was sharing of CT antigens between cell lines of the same tumor type and with cell lines of other gynecologic tumor types. Themeannumber of antigens shared amongendometrial cell lines (5.5) was higher than the one shared by the ovarian cancer cell lines (3.8) with their corresponding tumor type (P=0.0122). Conclusions: CT antigens are expressed in gynecologic cancers. No single antigen was universally expressed among all gynecologic cancer cell lines, although most expressed SP-17. Utilizing a multiepitope immunotherapy approach could provide a universal therapeutic option for gynecologic cancers.