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Article

Inducible Costimulator and Its Ligand Promote Proliferation and Migration of Tumor Cells in Cutaneous T-Cell Lymphoma

by
Kenta Oka
1,
Takuya Miyagawa
1,*,
Hiromichi Morita
1,
Hiraku Suga
1,
Tomomitsu Miyagaki
2,
Sayaka Shibata
1,
Hiroaki Kamijo
1,
Yuka Mizuno
1,
Teruyoshi Hisamoto
1,
Issei Omori
1,
Hikari Boki
1,
Tomonori Oka
1,
Naomi Takahashi-Shishido
1,
Makoto Sugaya
3 and
Shinichi Sato
1
1
Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
2
Department of Dermatology, St. Marianna University School of Medicine, Sugao, Miyamae-ku, Kanagawa 216-8511, Japan
3
Department of Dermatology, International University of Health and Welfare, Kouzunomori, Chiba 286-8686, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(3), 1408; https://doi.org/10.3390/ijms27031408
Submission received: 21 November 2025 / Revised: 13 January 2026 / Accepted: 28 January 2026 / Published: 30 January 2026
(This article belongs to the Special Issue Cutaneous Biology, Molecular Dermatology and Dermatopathology, 2nd Edition)
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Abstract

Inducible costimulator (ICOS) is a costimulatory immune checkpoint receptor expressed on activated T-cells, while the ICOS ligand (ICOSL) is expressed on antigen-presenting cells. The ICOS–ICOSL axis promotes the survival of memory and effector T-cells and induces several immune responses. In addition, the ICOS–ICOSL interaction induces cell proliferation, cell survival, and cytokine production. The roles of ICOS and ICOSL in cutaneous T-cell lymphoma (CTCL) are unclear. In this study, we examined the roles of ICOS and ICOSL in CTCL. The tumor cells co-expressed ICOS and ICOSL, and the upregulated expression of ICOS and ICOSL reflected disease severity. Anti-ICOS and anti-ICOSL neutralizing antibodies inhibited both the in vitro and in vivo proliferation of CTCL cell lines. The anti-ICOSL neutralizing antibodies induced apoptosis and suppressed CCR4 expression on tumor cells, inhibiting CCR4–CCL17-mediated migration. These results suggest that the ICOS–ICOSL axis plays an essential role in CTCL pathogenesis, and targeting the ICOS–ICOSL axis could be a viable strategy for treating CTCL.
Keywords: cutaneous T-cell lymphoma; inducible co-stimulator; inducible co-stimulator ligand; mycosis fungoides; Sézary syndrome; CCR4 cutaneous T-cell lymphoma; inducible co-stimulator; inducible co-stimulator ligand; mycosis fungoides; Sézary syndrome; CCR4

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MDPI and ACS Style

Oka, K.; Miyagawa, T.; Morita, H.; Suga, H.; Miyagaki, T.; Shibata, S.; Kamijo, H.; Mizuno, Y.; Hisamoto, T.; Omori, I.; et al. Inducible Costimulator and Its Ligand Promote Proliferation and Migration of Tumor Cells in Cutaneous T-Cell Lymphoma. Int. J. Mol. Sci. 2026, 27, 1408. https://doi.org/10.3390/ijms27031408

AMA Style

Oka K, Miyagawa T, Morita H, Suga H, Miyagaki T, Shibata S, Kamijo H, Mizuno Y, Hisamoto T, Omori I, et al. Inducible Costimulator and Its Ligand Promote Proliferation and Migration of Tumor Cells in Cutaneous T-Cell Lymphoma. International Journal of Molecular Sciences. 2026; 27(3):1408. https://doi.org/10.3390/ijms27031408

Chicago/Turabian Style

Oka, Kenta, Takuya Miyagawa, Hiromichi Morita, Hiraku Suga, Tomomitsu Miyagaki, Sayaka Shibata, Hiroaki Kamijo, Yuka Mizuno, Teruyoshi Hisamoto, Issei Omori, and et al. 2026. "Inducible Costimulator and Its Ligand Promote Proliferation and Migration of Tumor Cells in Cutaneous T-Cell Lymphoma" International Journal of Molecular Sciences 27, no. 3: 1408. https://doi.org/10.3390/ijms27031408

APA Style

Oka, K., Miyagawa, T., Morita, H., Suga, H., Miyagaki, T., Shibata, S., Kamijo, H., Mizuno, Y., Hisamoto, T., Omori, I., Boki, H., Oka, T., Takahashi-Shishido, N., Sugaya, M., & Sato, S. (2026). Inducible Costimulator and Its Ligand Promote Proliferation and Migration of Tumor Cells in Cutaneous T-Cell Lymphoma. International Journal of Molecular Sciences, 27(3), 1408. https://doi.org/10.3390/ijms27031408

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