{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T22:53:34Z","timestamp":1776207214054,"version":"3.50.1"},"reference-count":59,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["FSSF-2023-0046"],"award-info":[{"award-number":["FSSF-2023-0046"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cutaneous melanoma remains one of the most aggressive tumors, yet the role innate immunity plays in its progression remains poorly understood. Effector elements with high regulatory potential, capable of both promoting and inhibiting tumor growth\u2014mast cells (MCs), are of particular interest. This includes quantitatively characterizing the interactions between tryptase-positive mast cells (MCs) with atypical Melanin\u2014A+ cells and describing their spatial phenotype, in relation to the stage of cutaneous melanoma. A retrospective analysis was carried out on samples retrieved from 128 patients with cutaneous melanoma (AJCC 8th edition: IA\u2013IIID). Histological analysis, histochemistry (toluidine blue, Giemsa), and diplex \/multiplex IHC for tryptase and Melan-A were performed; as well as Fluorescence imaging, 3D reconstructions and quantitative mapping in QuPath v 0.6.0. Proximity was assessed by the nucleus-to-nucleus distance: &lt;10 \u03bcm (contact), 10\u201320 \u03bcm (paracrine zone), &gt;20 \u03bcm (out of interaction). The relative amount of MCs in the intratumoral zone was lower than in the intact dermis, with a simultaneous increase in their absolute density per mm2 in the melanoma microenvironment, maximum in the peritumoral area and most pronounced at stage II. Three types of interactions were identified: (i) juxtaposition without secretion, (ii) degranulation of MCs directed to tumor cells, (iii) melanosecretion of Melanin\u2014A+ cells directed towards MCs, followed by phagocytosis of melanocores. An inverse intratumoral connection between the number of MCs and the number of Melanin\u2014A+ cells was noted; MCs with elongated forms, extensive contacts and polarized tryptase secretion, including granule localization near\/at the nuclei of adjacent cells, were frequently observed. The obtained data indicate stage-region-dependent bidirectional cross-talk between melanin and MCs, forming tissue spatial signals, potentially useful as biomarkers and targets for personalized therapy.<\/jats:p>","DOI":"10.3390\/ijms262311313","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:02:07Z","timestamp":1763974927000},"page":"11313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Interactions Between Tryptase-Positive Mast Cells and Melanin-A+ Cells in the Microenvironment of Cutaneous Melanoma"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8347-4556","authenticated-orcid":false,"given":"Dmitrii","family":"Atiakshin","sequence":"first","affiliation":[{"name":"Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, RUDN University, 6 Miklukho-Maklaya St., 117198 Moscow, Russia"},{"name":"Research Institute of Experimental Biology and Medicine, Burdenko Voronezh State Medical University, 394036 Voronezh, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8447-2600","authenticated-orcid":false,"given":"Grigory","family":"Demyashkin","sequence":"additional","affiliation":[{"name":"National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Koroleva St. 4, 249036 Obninsk, Russia"},{"name":"Laboratory of Histology and Immunohistochemistry, Institute of Translational Medicine and Biotechnology, IM Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2073-3699","authenticated-orcid":false,"given":"Kirill","family":"Silakov","sequence":"additional","affiliation":[{"name":"Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, RUDN University, 6 Miklukho-Maklaya St., 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8127-7251","authenticated-orcid":false,"given":"Aleksandra","family":"Prikhodko","sequence":"additional","affiliation":[{"name":"Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, RUDN University, 6 Miklukho-Maklaya St., 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-7454","authenticated-orcid":false,"given":"Vladimir","family":"Shchekin","sequence":"additional","affiliation":[{"name":"Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, RUDN University, 6 Miklukho-Maklaya St., 117198 Moscow, Russia"},{"name":"National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Koroleva St. 4, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Alekhnovich","sequence":"additional","affiliation":[{"name":"Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, RUDN University, 6 Miklukho-Maklaya St., 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyudmila","family":"Grivtsova","sequence":"additional","affiliation":[{"name":"National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Koroleva St. 4, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6966-5962","authenticated-orcid":false,"given":"Demyan","family":"Davydov","sequence":"additional","affiliation":[{"name":"Columbia University, 116th and Broadway, New York, NY 10027, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2888-7999","authenticated-orcid":false,"given":"Ilya","family":"Klabukov","sequence":"additional","affiliation":[{"name":"National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Koroleva St. 4, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6154-9959","authenticated-orcid":false,"given":"Denis","family":"Baranovskii","sequence":"additional","affiliation":[{"name":"National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Koroleva St. 4, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergei","family":"Ivanov","sequence":"additional","affiliation":[{"name":"National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Koroleva St. 4, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0546-5280","authenticated-orcid":false,"given":"Daniel","family":"Elieh-Ali-Komi","sequence":"additional","affiliation":[{"name":"Institute of Allergology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Zu Berlin, 10117 Berlin, Germany"},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, 12803 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1142-7483","authenticated-orcid":false,"given":"Igor","family":"Buchwalow","sequence":"additional","affiliation":[{"name":"Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, RUDN University, 6 Miklukho-Maklaya St., 117198 Moscow, Russia"},{"name":"Institute for Hematopathology, Fangdieckstr. 75a, 22547 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4060-8355","authenticated-orcid":false,"given":"Markus","family":"Tiemann","sequence":"additional","affiliation":[{"name":"Institute for Hematopathology, Fangdieckstr. 75a, 22547 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey","family":"Kostin","sequence":"additional","affiliation":[{"name":"Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, RUDN University, 6 Miklukho-Maklaya St., 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"Shegay","sequence":"additional","affiliation":[{"name":"National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Koroleva St. 4, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey","family":"Kaprin","sequence":"additional","affiliation":[{"name":"National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Koroleva St. 4, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.47162\/RJME.64.1.05","article-title":"Assessment of tumoral and peritumoral 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