학술논문
Immunotherapy with 4-1BBL-Expressing iPS Cell‐Derived Myeloid Lines Amplifies Antigen-Specific T Cell Infiltration in Advanced Melanoma
Document Type
article
Author
Haruka Kuriyama; Satoshi Fukushima; Toshihiro Kimura; Hisashi Kanemaru; Azusa Miyashita; Etsuko Okada; Yosuke Kubo; Satoshi Nakahara; Aki Tokuzumi; Yuki Nishimura; Ikko Kajihara; Katsunari Makino; Jun Aoi; Shinichi Masuguchi; Hirotake Tsukamoto; Takashi Inozume; Rong Zhang; Tetsuya Nakatsura; Yasushi Uemura; Satoru Senju; Hironobu Ihn
Source
International Journal of Molecular Sciences, Vol 22, Iss 4, p 1958 (2021)
Subject
Language
English
ISSN
22041958
1422-0067
1661-6596
1422-0067
1661-6596
Abstract
We have established an immune cell therapy with immortalized induced pluripotent stem-cell–derived myeloid lines (iPS-ML). The benefits of using iPS-ML are the infinite proliferative capacity and ease of genetic modification. In this study, we introduced 4-1BBL gene to iPS-ML (iPS-ML-41BBL). The analysis of the cell-surface molecules showed that the expression of CD86 was upregulated in iPS-ML-41BBL more than that in control iPS-ML. Cytokine array analysis was performed using supernatants of the spleen cells that were cocultured with iPS-ML or iPS-ML-41BBL. Multiple cytokines that are beneficial to cancer immunotherapy were upregulated. Peritoneal injections of iPS-ML-41BBL inhibited tumor growth of peritoneally disseminated mouse melanoma and prolonged survival of mice compared to that of iPS-ML. Furthermore, the numbers of antigen-specific CD8+ T cells were significantly increased in the spleen and tumor tissues treated with epitope peptide-pulsed iPS-ML-41BBL compared to those treated with control iPS-ML. The number of CXCR6-positive T cells were increased in the tumor tissues after treatment with iPS-ML-41BBL compared to that with control iPS-ML. These results suggest that iPS-ML-41BBL could activate antigen-specific T cells and promote their infiltration into the tumor tissues. Thus, iPS-ML-41BBL may be a candidate for future immune cell therapy aiming to change immunological “cold tumor” to “hot tumor”.