期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 71, 期 1, 页码 189-201出版社
SPRINGER
DOI: 10.1007/s00262-021-02954-z
关键词
Glioma; Wilms tumor gene 1; Immunotherapy; Intra-tumor immune response; Cancer vaccine
资金
- JSPS KAKENHI [JP 16K20008, JP 25462257]
This study found that WT1 and HLA class I antigen expression in tumor cells significantly decreased after WT1 peptide vaccine treatment, and maintenance of WT1 expression during vaccination was associated with longer survival. High HLA class I antigen expression and low CD4(+)/CD8(+) TIL ratio in pre-vaccination samples were also linked to better outcomes. The number of infiltrating CD4(+) T cells decreased post-vaccination, providing insights into immune reactions during cancer immunotherapy.
We have previously revealed the overexpression of Wilms' tumor gene 1 (WT1) in malignant glioma and developed WT1 peptide vaccine cancer immunotherapy. A phase II clinical trial indicated the clinical efficacy of the WT1 peptide vaccine for recurrent malignant glioma. Here, we aimed to investigate the immunological microenvironment in glioma tissues before and after WT1 peptide vaccine treatment. Paired tissue samples were obtained from 20 malignant glioma patients who had received the WT1 peptide vaccine for > 3 months and experienced tumor progression, confirmed radiographically and/or clinically, during vaccination. We discovered that the expression of WT1 and HLA class I antigens in the tumor cells significantly decreased after vaccination. Maintenance of WT1 expression, which is the target molecule of immunotherapy, in tumor cells during the vaccination period was significantly associated with a longer progression-free and overall survival. A high expression of HLA class I antigens and low CD4(+)/CD8(+) tumor-infiltrating lymphocytes (TIL) ratio in pre-vaccination specimens, were also associated with a good prognosis. No statistically significant difference existed in the number of infiltrating CD3(+) or CD8(+) T cells between the pre- and post-vaccination specimens, whereas the number of infiltrating CD4(+) T cells significantly decreased in the post-vaccination specimens. This study provides insight into the mechanisms of intra-tumoral immune reaction/escape during WT1 peptide vaccine treatment and suggests potential clinical strategies for cancer immunotherapy.
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