Identification of an HLA-A2-restricted CD147 epitope that can induce specific CTL cytotoxicity against drug resistant MCF-7/Adr cells
Cluster of differentiation (CD)147 is highly expressed in drug-resistant tumor cell lines and is involved in the formation of tumor drug resistance. Therefore, immunotherapy utilizing CD147 epitope peptides is a promising approach for the elimination of drugresistant tumor cells. However, like most tumorassociated antigens (TAAs), CD147 belongs to the autoantigen category, and T cells that recognize high affinity, immunodominant epitopes from autoantigens are deleted though thymic negative selection. Furthermore, wildtype autoantigen peptides cannot effectively activate and expand T lymphocytes with lower affinity T cell receptors in vivo. However, mutations of TAA peptides have been demonstrated to increase the affinity of major histocompatibility complex molecules and their binding to T cell receptor molecules, leading to activation of T lymphocytes in vitro. In the present study, a highaffinity point mutation peptide, CD147126134L2, was predicted by the human leukocyte antigen (HLA) binding prediction algorithm and its affinity was testified using a T2 binding assay. In addition, when peptidespecific cytotoxic T lymphocytes (CTLs) were stimulated with dendritic cells loaded with the CD147126134L2 peptide under HLAA*02:01 restriction, interferonγ release and cytotoxicity assays showed that peptidespecific CTLs effectively crossrecognized and lysed T2 target cells loaded either with the wildtype (CD147126134) or mutated peptide (CD147126134L2). Moreover, the CD147126134L2 peptidespecific CTLs exerted strong cytotoxic activity against drugresistant MCF7/Adr cells, which express a high level of CD147 and are HLAA*02:01positive, but not against normal MCF7 cells. Thus, this suggests that the wildtype peptide (CD147126134) is naturally presented on HLAA*02:01 of CD147expressing MCF7/Adr cells and is crossrecognized by CTLs. In conclusion, an HLAA*02:01restricted CD147point mutant epitope peptide was identified that induces CTLs to efficiently lyse drugresistant MCF7 cells that highly express CD147. Therefore, this immunotherapeutic approach should be explored as a potential treatment for drug-resistant tumors.
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Document Type: Research Article
Affiliations: Guangdong Province Key Laboratory of Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China
Publication date: April 1, 2018
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- Oncology Letters is a monthly, peer-reviewed journal, available in print and online, that focuses on all aspects of clinical oncology, as well as in vitro and in vivo experimental model systems relevant to the mechanisms of disease.
The principal aim of Oncology Letters is to provide the prompt publication of original studies of high quality that pertain to clinical oncology, chemotherapy, oncogenes, carcinogenesis, metastasis, epidemiology and viral oncology in the form of original research, reviews and case reports.
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