Phosphorylated vimentin as an immunotherapeutic target against metastatic colorectal cancer

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 posttranslationally 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.

Vimentin Protein In Situ Expression Predicts Less Tumor Metastasis and Overall Better Survival of Endometrial Carcinoma

“…This suggests that lack of vimentin expression does not allow for its EMT function, and tumor metastasis may be promoted through other routes. Recently, some studies [ 31 – 35 ] have proposed vimentin as a potential molecular target for treatment of some kinds of cancers; however, our results suggest enough prudence in using it for EC.…”

Research Progress of Epithelial-mesenchymal Transition Treatment and Drug Resistance in Colorectal Cancer

“… 72 Phosphorylation of waveform proteins promotes the growth of metastatic tumors and the high expression of waveform proteins indicates the activation of EMT in malignant tumors. Ohara et al 73 reported that a novel phosphorylated helper peptide epitope in the waveform protein could induce sufficient T cell responses, suggesting that immunotherapy targeting phosphorylated waveform proteins could be a promising treatment strategy for patients with metastatic colorectal cancer.…”

A tumor metastasis‐associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity

“…Interestingly, we detected TWIST1 140–162 peptide‐specific production of not only IFN‐γ but also TNFα and granzyme B in the samples from BC5, BC6, and BC7, indicating that they showed a Th1 cell phenotype (Figure 4). As we had previously demonstrated that granzyme B‐producing HTLs directly killed tumor cells, 31,32 these TWIST1‐specific HTLs would show antitumor cytotoxicity. These results suggested that the TWIST1 140–162 peptide could effectively activate TWIST1‐specific HTLs to enhance cell‐mediated immunity against tumors expressing TWIST1/2.…”