Erschienen in:
21.02.2020 | Original Article
Phosphorylated vimentin as an immunotherapeutic target against metastatic colorectal cancer
verfasst von:
Mizuho Ohara, Kenzo Ohara, Takumi Kumai, Takayuki Ohkuri, Toshihiro Nagato, Yui Hirata-Nozaki, Akemi Kosaka, Marino Nagata, Ryusuke Hayashi, Shohei Harabuchi, Yuki Yajima, Kensuke Oikawa, Yasuaki Harabuchi, Yasuo Sumi, Hiroyuki Furukawa, Hiroya Kobayashi
Erschienen in:
Cancer Immunology, Immunotherapy
|
Ausgabe 6/2020
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Abstract
Colorectal cancer (CRC) patients with metastatic lesions have low 5-year survival rates. During metastasis, cancer cells often obtain unique characteristics such as epithelial–mesenchymal transition (EMT). Vimentin a biomarker contributes to EMT by changing cell shape and motility. Since abnormal phosphorylation is a hallmark of malignancy, targeting phosphorylated vimentin is a feasible approach for the treatment of metastatic tumors while sparing non-tumor cells. Recent evidence has revealed that both CD8 cytotoxic T lymphocytes (CTLs) and also CD4 helper T lymphocytes (HTLs) can distinguish post-translationally modified antigens from normal antigens. Here, we showed that the expression of phosphorylated vimentin was upregulated in metastatic sites of CRC. We also showed that a chemotherapeutic reagent augmented the expression of phosphorylated vimentin. The novel phosphorylated helper peptide epitopes from vimentin could elicit a sufficient T cell response. Notably, precursor lymphocytes that specifically reacted to these phosphorylated vimentin-derived peptides were detected in CRC patients. These results suggest that immunotherapy targeting phosphorylated vimentin could be promising for metastatic CRC patients.