{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T21:43:36Z","timestamp":1758404616309,"version":"3.37.3"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,10,26]],"date-time":"2017-10-26T00:00:00Z","timestamp":1508976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K10143"],"award-info":[{"award-number":["16K10143"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2018,1]]},"abstract":"Abstract<\/jats:title>Together with regulatory T cells (Tregs), tumor\u2010associated macrophages (TAM<\/jats:styled-content>s) play roles in maintaining the tumor microenvironment. Although cytotoxic antimelanoma drugs such as dacarbazine (DTIC<\/jats:styled-content>), nimustine hydrochloride (ACNU<\/jats:styled-content>) and vincristine (VCR<\/jats:styled-content>) have been used for the treatment of malignant melanoma as adjuvant therapy in Japan, the detailed mechanisms of their immunomodulatory effects are not fully understood. As the majority of TAM<\/jats:styled-content>s are alternatively activated M2 macrophages that favour tumor development, the aim of this study was to elucidate the immunomodulatory effects of these reagents on human monocyte\u2010derived M2 macrophages. First, mRNA<\/jats:styled-content> expressions and protein production of immune checkpoint molecules, PD<\/jats:styled-content>\u2010L1 and chemokines by CD<\/jats:styled-content>163+<\/jats:sup> CD<\/jats:styled-content>206+<\/jats:sup> M2 macrophages derived from peripheral blood mononuclear cells were investigated to determine the immunomodulatory effects of DTIC<\/jats:styled-content>, ACNU<\/jats:styled-content>, and VCR<\/jats:styled-content>. DTIC<\/jats:styled-content> and VCR<\/jats:styled-content> significantly decreased PD<\/jats:styled-content>\u2010L1 mRNA<\/jats:styled-content> expression, which was confirmed by flow cytometry. Moreover, the mRNA<\/jats:styled-content> expression and production of CCL<\/jats:styled-content>22 were significantly decreased by DTIC<\/jats:styled-content>, which suggested that DTIC<\/jats:styled-content> might suppress the recruitment of Tregs in the tumor site. Furthermore, the decreased expression of PD<\/jats:styled-content>\u2010L1 and production of CCL<\/jats:styled-content>22 were validated in vivo, using the B16F10 mouse melanoma model, leading to abrogation of the suppressive function of T\u2010cell proliferation. The present report suggests one of the possible antimelanoma mechanisms of DAV<\/jats:styled-content> combination chemotherapy for melanoma patients.<\/jats:p>","DOI":"10.1111\/exd.13417","type":"journal-article","created":{"date-parts":[[2017,8,20]],"date-time":"2017-08-20T10:26:35Z","timestamp":1503224795000},"page":"64-70","source":"Crossref","is-referenced-by-count":20,"title":["Cytotoxic antimelanoma drugs suppress the activation of M2 macrophages"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6809-5833","authenticated-orcid":false,"given":"Taku","family":"Fujimura","sequence":"first","affiliation":[{"name":"Department of Dermatology Tohoku University Graduate School of Medicine Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aya","family":"Kakizaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology Tohoku University Graduate School of Medicine Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumi","family":"Kambayashi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Tohoku University Graduate School of Medicine Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yota","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Dermatology Tohoku University Graduate School of Medicine Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayo","family":"Tanita","sequence":"additional","affiliation":[{"name":"Department of Dermatology Tohoku University Graduate School of Medicine Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunbing","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Tohoku University Graduate School of Medicine Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadanori","family":"Furudate","sequence":"additional","affiliation":[{"name":"Department of Dermatology Tohoku University Graduate School of Medicine Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Setsuya","family":"Aiba","sequence":"additional","affiliation":[{"name":"Department of Dermatology Tohoku University Graduate School of Medicine Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,10,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.53.0105"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.416"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2016.05.015"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3314"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131916"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.06.010"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07205"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.209"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2015.1047584"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.11.009"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2016.05.004"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4161\/2162402X.2014.978709"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000369166"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.12040"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.1998.tb02460.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"494","DOI":"10.2340\/0001555575494","volume":"75","author":"Nagatani T.","year":"1995","journal-title":"Acta Derm. 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