A tumor metastasis-associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity （TWIST1特異的ヘルパーT細胞の活性化を応用したがん免疫療法に関する研究）
著者
矢島, 優己
(Yajima, Yuki)
上位タイトル
Cancer science
Vol.113,
No.8
(2022.
8)
,p.2526-
2535
識別番号
ISSN
1347-9032
DOI
10.1111/cas.15429
その他
PMID:35579200
博士論文情報
学位授与番号
10107A583
学位授与年月日
2022-09-30
学位名
博士（医学）
学位授与機関
旭川医科大学
抄録
Although neoantigens are one of the most favorable targets in cancer immunotherapy, it is less versatile and costly to apply neoantigen-derived cancer vaccines to patients due to individual variation. It is, therefore, important to find highly immunogenic antigens between tumor-specific or associated antigens that are shared among patients. Considering the cancer immunoediting theory, immunogenic tumor cells cannot survive in the early phase of tumor progression including two processes: elimination and equilibrium. We hypothesized that highly immunogenic molecules are allowed to be expressed in tumor cells after an immune suppressive tumor microenvironment was established, if these molecules contribute to tumor survival. In the current study, we focused on TWIST1 as a candidate for highly immunogenic antigens because it is upregulated in tumor cells under hypoxia and promotes tumor metastasis, which is observed in the late phase of tumor progression. We demonstrated that TWIST1 had an immunogenic peptide sequence TWIST1140-162 , which effectively activated TWIST1-specific CD4+ T-cells. In a short-term culture system, we detected more TWIST1-specific responses in breast cancer patients compared with in healthy donors. Vaccination with the TWIST1 peptide also showed efficient expansion of TWIST1-reactive HTLs in humanized mice. These findings indicate that TWIST1 is a highly immunogenic shared antigen and a favorable target for cancer immunotherapy.
