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Immunol."],"abstract":"<jats:p>Soft tissue sarcomas (STS) encompass over 50 histologic subtypes, representing more than 1% of solid tumors. Standard treatments include surgical resection and therapies such as anthracyclines or trabectedin for advanced cases, though challenges persist due to the tumor microenvironment\u2019s complexity and limited immune profiling data. This study evaluates Trabectedin therapy in 22 refractory STS patients, analyzing progression-free survival (PFS) and immune responses. Immune monitoring included deep immunophenotyping (200+ parameters), gene expression profiling (103 genes), and soluble proteome analysis (99 analytes). Using RECIST1.1 criteria, 68.2% of patients achieved stable disease (SD), while 31.8% exhibited progression disease (PD). Therapy duration revealed 59.1% treated for less than 12 months (&amp;lt;12M) and 40.9% for 12 or more months (\u226512M). A significant PFS improvement was observed in SD versus PD patients (p=0.0154), while therapy duration showed no effect (p=0.5433). PD patients showed reduced eosinophils (p&amp;lt;0.05) and Th2 cells (p&amp;lt;0.05). Gene expression analysis identified changes in BTRC (decreased), IFNA1 (increased), and IL9 (increased) in PD versus SD patients (p&amp;lt;0.05). Patients treated \u226512M exhibited increased activated HLA-DR Th2 cells (p&amp;lt;0.05) and decreased exhausted B cells and NK cell subsets (p&amp;lt;0.05). Principal component and hierarchical clustering analyses identified distinct immune profiles associated with RECIST1.1 and therapy duration, underscoring immune profiling\u2019s role in understanding treatment responses. These findings support further research into immune monitoring for future clinical trials.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1516793","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T05:10:49Z","timestamp":1739250649000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Immune monitoring of trabectedin therapy in refractory soft tissue sarcoma patients - the IMMUNYON study"],"prefix":"10.3389","volume":"16","author":[{"given":"Paulo","family":"Rodrigues-Santos","sequence":"first","affiliation":[]},{"given":"Jani Sofia","family":"Almeida","sequence":"additional","affiliation":[]},{"given":"Luana Madalena","family":"Sousa","sequence":"additional","affiliation":[]},{"given":"Patr\u00edcia","family":"Couceiro","sequence":"additional","affiliation":[]},{"given":"Ant\u00f3nio","family":"Martinho","sequence":"additional","affiliation":[]},{"given":"Joana","family":"Rodrigues","sequence":"additional","affiliation":[]},{"given":"Ruben","family":"Fonseca","sequence":"additional","affiliation":[]},{"given":"Manuel","family":"Santos-Rosa","sequence":"additional","affiliation":[]},{"given":"Paulo","family":"Freitas-Tavares","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 Manuel","family":"Casanova","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4161\/21645515.2014.983003","article-title":"Potential for immunotherapy in soft tissue sarcoma","volume":"10","author":"Tseng","year":"2014","journal-title":"Hum Vaccin Immunother"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2015.1076792","article-title":"Targeted therapy and promising novel agents for the treatment of advanced soft tissue sarcomas","volume":"24","author":"Mohindra","year":"2015","journal-title":"Expert Opin Investig Drugs"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31517","article-title":"Rationale and emerging strategies for immune checkpoint blockade in soft tissue sarcoma","volume":"124","author":"Wisdom","year":"2018","journal-title":"Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2020.0058","article-title":"NCCN guidelines insights: soft tissue sarcoma, version 1.2021","volume":"18","author":"von Mehren","year":"2020","journal-title":"J Natl Compr Canc Netw"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-020-02534-0","article-title":"SEOM Clinical Guideline of management of soft-tissue sarcoma (2020)","volume":"23","author":"de Juan Ferr\u00e9","year":"2021","journal-title":"Clin Transl Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2022.2152324","article-title":"What's the latest with investigational drugs for soft tissue sarcoma","volume":"31","author":"Cojocaru","year":"2022","journal-title":"Expert Opin Investig Drugs"},{"key":"B7","doi-asserted-by":"publisher","first-page":"13","DOI":"10.2217\/fon-2022-0518","article-title":"Trabectedin as second-line treatment in advanced soft tissue sarcoma: quality of life and safety outcomes","volume":"18","author":"Grignani","year":"2022","journal-title":"Future Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.777872","article-title":"The role of trabectedin in soft tissue sarcoma","volume":"13","author":"Nakamura","year":"2022","journal-title":"Front Pharmacol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3747\/co.27.5475","article-title":"Update on systemic therapy for advanced soft-tissue sarcoma","volume":"27","author":"Smrke","year":"2020","journal-title":"Curr Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2174\/092986709788803312","article-title":"Doxorubicin: the good, the bad and the ugly effect","volume":"16","author":"Carvalho","year":"2009","journal-title":"Curr Med Chem"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2019.110834","article-title":"An update on the mechanisms related to cell death and toxicity of doxorubicin and the protective role of nutrients","volume":"134","author":"Varela-L\u00f3pez","year":"2019","journal-title":"Food Chem Toxicol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1039\/b808331m","article-title":"Development of yondelis\u00ae (Trabectedin, ET-743). 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