TY - JOUR
T1 - Identification of a HLA-A*0201-restricted immunogenic epitope from the universal tumor antigen DEPDC1
AU - Tosi, Anna
AU - Dalla Santa, Silvia
AU - Cappuzzello, Elisa
AU - Marotta, Carolina
AU - Walerich, Dawid
AU - Del Sal, Giannino
AU - Zanovello, Paola
AU - Sommaggio, Roberta
AU - Rosato, Antonio
PY - 2017/8/3
Y1 - 2017/8/3
N2 - The identification of universal tumor-specific antigens 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, resistance to induction of apoptosis and cell invasion, suggesting that it may play key roles in the oncogenic process. In this study, we report that DEPDC1 expression is upregulated in most 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 a HLA-A*0201 allele-restricted immunogenic DEPDC1-derived epitope, which is able to induce cytotoxic T lymphocytes (CTL) exerting a strong and specific functional response in vitro toward not only peptide-loaded cells but also 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 evidence that this DEPDC1-derived antigenic epitope can be exploited as a new tool for developing immunotherapeutic strategies for HLA-A*0201 patients with TNBC, and potentially many other cancers.
AB - The identification of universal tumor-specific antigens 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, resistance to induction of apoptosis and cell invasion, suggesting that it may play key roles in the oncogenic process. In this study, we report that DEPDC1 expression is upregulated in most 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 a HLA-A*0201 allele-restricted immunogenic DEPDC1-derived epitope, which is able to induce cytotoxic T lymphocytes (CTL) exerting a strong and specific functional response in vitro toward not only peptide-loaded cells but also 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 evidence that this DEPDC1-derived antigenic epitope can be exploited as a new tool for developing immunotherapeutic strategies for HLA-A*0201 patients with TNBC, and potentially many other cancers.
KW - Cancer immunotherapy
KW - cytotoxic T lymphocytes
KW - DEPDC1
KW - triple negative breast cancer
KW - tumor antigen
UR - http://www.scopus.com/inward/record.url?scp=85020738238&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020738238&partnerID=8YFLogxK
U2 - 10.1080/2162402X.2017.1313371
DO - 10.1080/2162402X.2017.1313371
M3 - Article
AN - SCOPUS:85020738238
VL - 6
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 8
M1 - e1313371
ER -