{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:16:44Z","timestamp":1790108204887,"version":"4.0.1"},"reference-count":53,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Scientific Foundation","award":["23-65-00003"],"award-info":[{"award-number":["23-65-00003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pleomorphic rhabdomyosarcoma is a rare soft-tissue tumor that occupies an uncertain middle ground between rhabdomyosarcoma and undifferentiated pleomorphic sarcoma. With its relative rarity, aggressiveness, and lack of detailed characterization, it presents a challenging task for therapeutic treatment. In this case study, we use single-cell transcriptomics to investigate the heterogeneous landscape of pRMS and the tumor microenvironment. We demonstrate that the tumor populations in pRMS have a clear division into myogenic and non-myogenic clusters, with the non-myogenic clusters having more numerous communication links with the immune populations. All pRMS tumor clusters use the MIF-CD74 pathway to suppress the immune response, while APP, PTN, and CXCL12 signaling are employed predominantly by the non-myogenic tumor clusters. The cytotoxic T cells in pRMS bear markers of exhaustion (LAG3, HAVCR2, EOMES), and the macrophages express myeloid checkpoint-related genes (SIGLEC1, SIRPA, CSF1R, HAVCR2). This transcriptomic data suggests that targeting MIF and APP signaling in pRMS may have therapeutic potential; however, studies on multiple-patient cohorts, protein verification, and in vitro and in vivo validation are still needed for clinical actionability.<\/jats:p>","DOI":"10.3390\/ijms262311420","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:04:57Z","timestamp":1764151497000},"page":"11420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Single-Cell Sequencing Reveals Novel Tumor Populations and Their Interplay with the Immune Microenvironment in a Pleomorphic Rhabdomyosarcoma"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5618-4588","authenticated-orcid":false,"given":"Elena E.","family":"Kopantseva","sequence":"first","affiliation":[{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 115093 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6514-3997","authenticated-orcid":false,"given":"Alexander V.","family":"Ikonnikov","sequence":"additional","affiliation":[{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 115093 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim E.","family":"Menyailo","sequence":"additional","affiliation":[{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 115093 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timur I.","family":"Fetisov","sequence":"additional","affiliation":[{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 115093 Moscow, Russia"},{"name":"N.N. Blokhin National Medical Research Center of Oncology, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia A.","family":"Korobeynikova","sequence":"additional","affiliation":[{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 115093 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8599-6833","authenticated-orcid":false,"given":"Kirill I.","family":"Kirsanov","sequence":"additional","affiliation":[{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 115093 Moscow, Russia"},{"name":"N.N. Blokhin National Medical Research Center of Oncology, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5548-3295","authenticated-orcid":false,"given":"Anastasia A.","family":"Tararykova","sequence":"additional","affiliation":[{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 115093 Moscow, Russia"},{"name":"N.N. Blokhin National Medical Research Center of Oncology, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beniamin Yu.","family":"Bokhyan","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay A.","family":"Kozlov","sequence":"additional","affiliation":[{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 115093 Moscow, Russia"},{"name":"N.N. Blokhin National Medical Research Center of Oncology, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9710-8178","authenticated-orcid":false,"given":"Marianna G.","family":"Yakubovskaya","sequence":"additional","affiliation":[{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 115093 Moscow, Russia"},{"name":"N.N. Blokhin National Medical Research Center of Oncology, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2923-9755","authenticated-orcid":false,"given":"Evgeny V.","family":"Denisov","sequence":"additional","affiliation":[{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 115093 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"953","DOI":"10.5858\/arpa.2021-0183-RA","article-title":"An Integrative Morphologic and Molecular Approach for Diagnosis and Subclassification of Rhabdomyosarcoma","volume":"146","author":"Fan","year":"2022","journal-title":"Arch. Pathol. Lab. 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