Identification of a HLA-A*0201-restricted immunogenic epitope from the universal tumor antigen DEPDC1

The identification of universal tumor-specific antigens (TSA) shared between multiple patients and/or multiple tumors is of great importance to overcome the practical limitations of personalized cancer immunotherapy. Recent studies support the involvement of DEPDC1 in many aspects of cancer traits, such as cell proliferation, anti-apoptosis and cell invasion, suggesting that it may play key roles in the oncogenic process. In this study, we report that DEPDC1 expression is up-regulated in several types of human tumors, and closely linked to a poorer prognosis; therefore, it might be regarded as a novel universal oncoantigen potentially suitable for targeting many different cancers. In this regard, we report the identification of an immunogenic DEPDC1-derived epitope restricted for the HLA-A*0201 molecule, which is able to induce cytotoxic T lymphocytes (CTL) exerting a strong and specific functional response in vitro in response not only to peptide-loaded cells but also to triple negative breast cancer (TNBC) cells endogenously expressing the DEPDC1 protein. Such CTL are also therapeutically active against human TNBC xenografts in vivo upon adoptive transfer in immunodeficient mice. Overall, these data provide evidences that this DEPDC1-derived antigenic epitope can be exploited as a new tool for the development of immunotherapeutic strategies for HLA-A*0201 patients with TNBC, and potentially many other cancers. Moreover, we plan to employ an approach of multiplexing digital pathology to study the intimate relationships that adoptively transferred lymphocytes can establish with TNBC cells in tumor-bearing mice, as further advances in immunotherapy approaches require a detailed understanding of cell dynamics within the tumor microenvironment. The benefits of multispectral immunohistochemistry, combined with the development of software for quantitation, are making this methodology an increasingly powerful tool in the analysis and characterization of tissue and cellular processes, supporting diagnostic potential in order to improve therapies.