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Immunotherapy with 4-1BBL-Expressing iPS Cell‐Derived Myeloid Lines Amplifies Antigen-Specific T Cell Infiltration in Advanced Melanoma

Authors :
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)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

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”.

Details

Language :
English
ISSN :
22041958, 14220067, and 16616596
Volume :
22
Issue :
4
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.f921cc729da4155a4382b4092d3f07a
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms22041958