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2017 ; 6
(8
): e1313371
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Identification of a HLA-A*0201-restricted immunogenic epitope from the universal
tumor antigen DEPDC1
#MMPMID28919988
Tosi A
; Dalla Santa S
; Cappuzzello E
; Marotta C
; Walerych D
; Del Sal G
; Zanovello P
; Sommaggio R
; Rosato A
Oncoimmunology
2017[]; 6
(8
): e1313371
PMID28919988
show ga
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.