Identification of an HLA-A2-restricted CD147 epitope that can induce specific CTL cytotoxicity against drug resistant MCF-7/Adr cells

Author：Chuang Qu, Shuhui Gao, Hongwei Shao, Wenfeng Zhang, Huabben Bo, Xin Lu, Tianjiao Chen, Jing Kou, Yue Wang, Gui Si Chen, Shulin Huang, Han Shen   《Oncology Letters》

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ABSTRACTS

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 drug?resistant tumor cells. However, like most tumor?associated 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, wild?type autoantigen peptides cannot effectively activate and expand T lymphocytes with lower af?nity 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 high?affinity point mutation peptide, CD147126?134L2, was predicted by the human leukocyte antigen (HLA) binding prediction algorithm and its affinity was testified using a T2 binding assay. In addition, when peptide?specific cytotoxic T lymphocytes (CTLs) were stimulated with dendritic cells loaded with the CD147126?134L2 peptide under HLA?A*02:01 restriction, interferon?γ release and cytotoxicity assays showed that peptide?specific CTLs effectively cross?recognized and lysed T2 target cells loaded either with the wild?type (CD147126?134) or mutated peptide (CD147126?134L2). Moreover, the CD147126?134L2 peptide?specific CTLs exerted strong cytotoxic activity against drug?resistant MCF?7/Adr cells, which express a high level of CD147 and are HLA?A*02:01?positive, but not against normal MCF?7 cells. Thus, this suggests that the wild?type peptide (CD147126?134) is naturally presented on HLA?A*02:01 of CD147?expressing MCF?7/Adr cells and is cross?recognized by CTLs. In conclusion, an HLA?A*02:01?restricted CD147?point mutant epitope peptide was identified that induces CTLs to efficiently lyse drug?resistant MCF?7 cells that highly express CD147. Therefore, this immunotherapeutic approach should be explored as a potential treatment for drug-resistant tumors.

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https://www.spandidos-publications.com/ol/15/4/6050?text=fulltext