Objective: Immunotherapy has become one of the novel therapeutic strategies under investigation for several cancers including ovarian cancer. Although antigenic targets for the immune system exist in the form of tumor-associated antigens, no tumor-specific antigens have been identified for gynecological 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. Current data from gene expression profiles in many types of tumors suggests that antigen sharing between allogeneic tumors may be a generalizable phenomenon. We hypothesize that there will be antigen sharing between gynecological cancers. The aim of our study was to evaluate the expression of a panel of 20 CT antigens in gynecological tumor cell lines, and to determine if antigen sharing occurs among different gynecologic cancers.
Methods: RNA was isolated from 16 gynecological cancer cell lines (9 epithelial ovarian cancer, 8 endometrial cancer, 1 cervical cancer and 1 leiomyosarcoma cell line). Real time-PCR analysis was performed to determine the expression level of 20 CT antigens, including NY-ESO-1, MAGE-A3/A4, GAGE, LAGE, PIWIL-2, CT-45.
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 leyomyosarcoma 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%), PIWIL-2 (56.3%) and GAGE (56.3%). CT45, SP-17 and MAGE-A4 were expressed among all gynecological cancers. We found that different gynecological 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 gynecological tumor types. The mean number of antigens shared among endometrial cell lines (5.5) was higher than the one shared by the ovarian cancer cell lines (3.8) with their corresponding tumor type (p-value= 0.0122).
Conclusion: Cancer-testis antigens are expressed in gynecological cancers. No single antigen was noted universally expressed among all gynecological cancer cell lines, however most expressed SP-17. Utilizing a multiepitope immunotherapy approach could provide a universal therapeutic option for gynecological cancers.
Citation Format: Arlene E. Garcia-Soto, Tulay Koru-Sengul, Feng Miao, Taylor Schreiber, Wilberto Nieves-Neira, Eckhard Podack. Cancer-testis antigen expression is shared among gynecological tumors. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr A24.