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Erschienen in: Cancer Immunology, Immunotherapy 6/2020

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.
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Metadaten
Titel
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
Publikationsdatum
21.02.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 6/2020
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-020-02524-9

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