{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T08:05:25Z","timestamp":1777363525596,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013ICOSL axis promotes the survival of memory and effector T-cells and induces several immune responses. In addition, the ICOS\u2013ICOSL 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\u2013CCL17-mediated migration. These results suggest that the ICOS\u2013ICOSL axis plays an essential role in CTCL pathogenesis, and targeting the ICOS\u2013ICOSL axis could be a viable strategy for treating CTCL.<\/jats:p>","DOI":"10.3390\/ijms27031408","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T14:35:46Z","timestamp":1769783746000},"page":"1408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inducible Costimulator and Its Ligand Promote Proliferation and Migration of Tumor Cells in Cutaneous T-Cell Lymphoma"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6412-9570","authenticated-orcid":false,"given":"Kenta","family":"Oka","sequence":"first","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4471-1635","authenticated-orcid":false,"given":"Takuya","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromichi","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4212-8278","authenticated-orcid":false,"given":"Hiraku","family":"Suga","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-3128","authenticated-orcid":false,"given":"Tomomitsu","family":"Miyagaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, St. Marianna University School of Medicine, Sugao, Miyamae-ku, Kanagawa 216-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayaka","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Kamijo","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuka","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7105-5066","authenticated-orcid":false,"given":"Teruyoshi","family":"Hisamoto","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1059-898X","authenticated-orcid":false,"given":"Issei","family":"Omori","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hikari","family":"Boki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7362-3207","authenticated-orcid":false,"given":"Tomonori","family":"Oka","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0429-9033","authenticated-orcid":false,"given":"Naomi","family":"Takahashi-Shishido","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1618-329X","authenticated-orcid":false,"given":"Makoto","family":"Sugaya","sequence":"additional","affiliation":[{"name":"Department of Dermatology, International University of Health and Welfare, Kouzunomori, Chiba 286-8686, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3768","DOI":"10.1182\/blood-2004-09-3502","article-title":"WHO-EORTC classification for cutaneous 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