Phosphorylated vimentin as an immunotherapeutic target against metastatic colorectal cancer （リン酸化ビメンチンを標的とした大腸癌に対する腫瘍反応性ヘルパーT細胞応答に関する研究）
著者
大原, みずほ
(Ohara, Mizuho)
上位タイトル
Cancer immunology and immunotherapy CII
Vol.69,
No.6
(2020.
6)
,p.989-
999
識別番号
ISSN
0340-7004
DOI
10.1007/s00262-020-02524-9
その他
PMID:32086539
博士論文情報
学位授与番号
10107A585
学位授与年月日
2022-12-23
学位名
博士（医学）
学位授与機関
旭川医科大学
抄録
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.
