{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:13:12Z","timestamp":1785330792652,"version":"3.55.0"},"reference-count":173,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Pediatric oral rhabdomyosarcoma (RMS) is a rare and aggressive cancer of the head and neck, characterized by a complex and mostly immunosuppressive tumor\u2013immune microenvironment. Unlike adult cancers, pediatric RMS typically exhibits a \u201ccold\u201d immune profile, characterized by minimal T-cell infiltration, a low mutational burden, and resistance to immune checkpoint blockade. The tumor\u2019s location in the oral cavity adds difficulty to treatment because of anatomical and functional limitations. Additionally, the presence of fusion oncogenes, such as PAX3:FOXO1, hampers immunogenicity and treatment response by disrupting antigen presentation and reducing immune cell infiltration. Advances in immuno-oncology have introduced new strategies, including immune checkpoint inhibitors, chimeric antigen receptor (CAR) therapies, cancer vaccines, and oncolytic viruses. However, these approaches face specific challenges in the pediatric population due to developmental immune factors. This narrative review highlights recent findings on the immunobiology of pediatric oral RMS, focusing on tumor\u2013immune interactions and their impact on disease progression and treatment resistance. We reviewed the cellular components of the TIME, the mechanisms of immune evasion, and the expression of immune checkpoints, including PD-L1 and B7-H3. Emerging immunotherapies, including CAR-T, CAR-NK, and CAR-CIK cell therapies; checkpoint inhibitors; oncolytic viruses; and cancer vaccines, are discussed, with an emphasis on their current limitations and potential to transform the pediatric RMS immune landscape.<\/jats:p>","DOI":"10.3390\/children12091249","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T11:00:00Z","timestamp":1758106800000},"page":"1249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tumor\u2013Immune Interactions in Pediatric Oral Rhabdomyosarcoma: A Narrative Review on Immuno-Oncology and Emerging Therapies"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1069-6374","authenticated-orcid":false,"given":"Omar A.","family":"El Meligy","sequence":"first","affiliation":[{"name":"Pediatric Dentistry and Dental Public Health Department, Faculty of Dentistry, Alexandria University, Alexandria 21131, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3586-6731","authenticated-orcid":false,"given":"Noha M.","family":"Elemam","sequence":"additional","affiliation":[{"name":"Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates"},{"name":"Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0613-9161","authenticated-orcid":false,"given":"Wael A.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates"},{"name":"Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates"},{"name":"Department of Pathology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5259-327X","authenticated-orcid":false,"given":"Iman M.","family":"Talaat","sequence":"additional","affiliation":[{"name":"Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates"},{"name":"Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates"},{"name":"Pathology Department, Faculty of Medicine, Alexandria University, Alexandria 21131, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pathania, A.S. 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