Abstract 2694: DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is a CD133+ tumor-specific protein and induces antitumor immunity
Authors: Koshio Jun , Kagamu Hiroshi , Ichikawa Kosuke , Baba Junko , Saida Yu , Watanabe Satoshi , Tanaka Junta , Tanaka Hiroshi , Yoshizawa Hirohisa , Narita Ichiei 
Published: June 2012

Cancer cells that exclusively maintain the ability of self-renewal and differentiation are termed cancer stem cells (CSCs). It is still controversial if the classical CSC hierarchy exists in all of solid tumors, however, accumulating evidence suggests that heterogeneity within cancer cells exists and that cancer survives as the cells with CSC features during potentially lethal stresses, including chemotherapy, radiation treatment, and molecular targeting therapy. Although it is necessary to eradicate CSCs to obtain cure of cancer, effective treatment has not been elucidated. Interestingly, most of the identified immunogenic tumor antigens are cancer/testis (CT) antigens. One of the reasons why CT antigens are immunogenic is that they are unlikely to maintain peripheral tolerance, owing to restricted expression in the testis and in immortal malignant cells, because Tregs are maintained with antigen stimulation by dendritic cells (DCs) that acquire dying cells in the steady state. Since CSCs are highly immortal, it is possible that they possess immunogenic antigens that are not expressed in differentiated cancer cells or normal epithelial cells, and that these antigens may be ideal therapeutic targets for cancer treatment. Recently it was reported that CT antigens are mainly expressed in CSCs.

We isolated CD133+ tumor cells, which possessed CSC properties, from B16 melanoma cells. We found that CSC-specific LN T cells primed by the CD133+ tumor vaccine mediated potent antitumor therapeutic efficacy by eradicating CSCs in tumor, thereby curing parental melanomas that comprised &lt;1% CSCs. Interestingly, CD133+ tumor antigens tended to prime type 17 helper T (Th17) cells and Th1 cells, but not Th2 cells. Our proteome analyses revealed that DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked (DDX3X) is one of CD133+ melanoma-specific proteins. B16 tumor cells didn't lose CD133 expression by DDX3X knock down but lost the ability to proliferate in an anchoring independent manner. We examined DDX3X expression in 6 human cancer cell lines. HCT116 (colon cancer), and 87.5 (small cell lung cancer), were CD133+ and S2 (small cell lung cancer), A549 (lung cancer), PC9 (lung cancer), and WM115 (melanoma) were CD133-. HCT116 and 87.5 expressed DDX3X but all of other CD133- cancer cells didn't. The LN T cells draining DDX3X vaccines exhibited specific IFNγ and IL-17 release upon CD133+ tumor stimulation. A DDX3X vaccination induced antitumor protective immunity against parental melanoma. These results indicate that anti-CSC, especially anti-DDX3X, immunotherapy is a promising treatment option in the clinical setting.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2694. doi:10.1158/1538-7445.AM2011-2694