Immune monitoring of trabectedin therapy in refractory soft tissue sarcoma patients - the IMMUNYON study
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’s complexity...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1516793/full |
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| author | Paulo Rodrigues-Santos Paulo Rodrigues-Santos Paulo Rodrigues-Santos Paulo Rodrigues-Santos Paulo Rodrigues-Santos Paulo Rodrigues-Santos Jani Sofia Almeida Jani Sofia Almeida Jani Sofia Almeida Jani Sofia Almeida Jani Sofia Almeida Jani Sofia Almeida Luana Madalena Sousa Luana Madalena Sousa Luana Madalena Sousa Patrícia Couceiro Patrícia Couceiro Patrícia Couceiro Patrícia Couceiro António Martinho Joana Rodrigues Ruben Fonseca Manuel Santos-Rosa Manuel Santos-Rosa Manuel Santos-Rosa Manuel Santos-Rosa Manuel Santos-Rosa Paulo Freitas-Tavares José Manuel Casanova José Manuel Casanova José Manuel Casanova José Manuel Casanova José Manuel Casanova |
| author_facet | Paulo Rodrigues-Santos Paulo Rodrigues-Santos Paulo Rodrigues-Santos Paulo Rodrigues-Santos Paulo Rodrigues-Santos Paulo Rodrigues-Santos Jani Sofia Almeida Jani Sofia Almeida Jani Sofia Almeida Jani Sofia Almeida Jani Sofia Almeida Jani Sofia Almeida Luana Madalena Sousa Luana Madalena Sousa Luana Madalena Sousa Patrícia Couceiro Patrícia Couceiro Patrícia Couceiro Patrícia Couceiro António Martinho Joana Rodrigues Ruben Fonseca Manuel Santos-Rosa Manuel Santos-Rosa Manuel Santos-Rosa Manuel Santos-Rosa Manuel Santos-Rosa Paulo Freitas-Tavares José Manuel Casanova José Manuel Casanova José Manuel Casanova José Manuel Casanova José Manuel Casanova |
| author_sort | Paulo Rodrigues-Santos |
| collection | DOAJ |
| description | 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’s 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 (<12M) and 40.9% for 12 or more months (≥12M). 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<0.05) and Th2 cells (p<0.05). Gene expression analysis identified changes in BTRC (decreased), IFNA1 (increased), and IL9 (increased) in PD versus SD patients (p<0.05). Patients treated ≥12M exhibited increased activated HLA-DR Th2 cells (p<0.05) and decreased exhausted B cells and NK cell subsets (p<0.05). Principal component and hierarchical clustering analyses identified distinct immune profiles associated with RECIST1.1 and therapy duration, underscoring immune profiling’s role in understanding treatment responses. These findings support further research into immune monitoring for future clinical trials. |
| format | Article |
| id | doaj-art-fb7b3c5e52ac4a198315fc1addbfa26d |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-fb7b3c5e52ac4a198315fc1addbfa26d2025-02-11T05:10:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15167931516793Immune monitoring of trabectedin therapy in refractory soft tissue sarcoma patients - the IMMUNYON studyPaulo Rodrigues-Santos0Paulo Rodrigues-Santos1Paulo Rodrigues-Santos2Paulo Rodrigues-Santos3Paulo Rodrigues-Santos4Paulo Rodrigues-Santos5Jani Sofia Almeida6Jani Sofia Almeida7Jani Sofia Almeida8Jani Sofia Almeida9Jani Sofia Almeida10Jani Sofia Almeida11Luana Madalena Sousa12Luana Madalena Sousa13Luana Madalena Sousa14Patrícia Couceiro15Patrícia Couceiro16Patrícia Couceiro17Patrícia Couceiro18António Martinho19Joana Rodrigues20Ruben Fonseca21Manuel Santos-Rosa22Manuel Santos-Rosa23Manuel Santos-Rosa24Manuel Santos-Rosa25Manuel Santos-Rosa26Paulo Freitas-Tavares27José Manuel Casanova28José Manuel Casanova29José Manuel Casanova30José Manuel Casanova31José Manuel Casanova32Laboratory of Immunology and Oncology, Center for Neurosciences and Cell Biology (CNC), University of Coimbra, Coimbra, PortugalInstitute of Immunology, University of Coimbra, Faculty of Medicine (FMUC), Coimbra, PortugalCenter for Investigation in Environment, Genetics and Oncobiology (CIMAGO), University of Coimbra, Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, PortugalCenter for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, PortugalClinical and Academic Centre of Coimbra (CACC), Coimbra, PortugalLaboratory of Immunology and Oncology, Center for Neurosciences and Cell Biology (CNC), University of Coimbra, Coimbra, PortugalInstitute of Immunology, University of Coimbra, Faculty of Medicine (FMUC), Coimbra, PortugalCenter for Investigation in Environment, Genetics and Oncobiology (CIMAGO), University of Coimbra, Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, PortugalCenter for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, PortugalClinical and Academic Centre of Coimbra (CACC), Coimbra, PortugalLaboratory of Immunology and Oncology, Center for Neurosciences and Cell Biology (CNC), University of Coimbra, Coimbra, PortugalCenter for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, PortugalClinical and Academic Centre of Coimbra (CACC), Coimbra, PortugalLaboratory of Immunology and Oncology, Center for Neurosciences and Cell Biology (CNC), University of Coimbra, Coimbra, PortugalCenter for Investigation in Environment, Genetics and Oncobiology (CIMAGO), University of Coimbra, Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, PortugalCenter for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, PortugalBlood and Transplantation Center of Coimbra, Portuguese Institute for Blood and Transplantation (IPST), Coimbra, PortugalTumor Unit of the Locomotor Apparatus, University Clinic of Orthopedics, Orthopedics Oncology Service, Coimbra Local Health Unit (ULSC), Coimbra, PortugalTumor Unit of the Locomotor Apparatus, University Clinic of Orthopedics, Orthopedics Oncology Service, Coimbra Local Health Unit (ULSC), Coimbra, PortugalInstitute of Immunology, University of Coimbra, Faculty of Medicine (FMUC), Coimbra, PortugalCenter for Investigation in Environment, Genetics and Oncobiology (CIMAGO), University of Coimbra, Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, PortugalCenter for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, PortugalClinical and Academic Centre of Coimbra (CACC), Coimbra, PortugalTumor Unit of the Locomotor Apparatus, University Clinic of Orthopedics, Orthopedics Oncology Service, Coimbra Local Health Unit (ULSC), Coimbra, PortugalCenter for Investigation in Environment, Genetics and Oncobiology (CIMAGO), University of Coimbra, Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, PortugalCenter for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, PortugalClinical and Academic Centre of Coimbra (CACC), Coimbra, PortugalTumor Unit of the Locomotor Apparatus, University Clinic of Orthopedics, Orthopedics Oncology Service, Coimbra Local Health Unit (ULSC), Coimbra, PortugalSoft 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’s 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 (<12M) and 40.9% for 12 or more months (≥12M). 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<0.05) and Th2 cells (p<0.05). Gene expression analysis identified changes in BTRC (decreased), IFNA1 (increased), and IL9 (increased) in PD versus SD patients (p<0.05). Patients treated ≥12M exhibited increased activated HLA-DR Th2 cells (p<0.05) and decreased exhausted B cells and NK cell subsets (p<0.05). Principal component and hierarchical clustering analyses identified distinct immune profiles associated with RECIST1.1 and therapy duration, underscoring immune profiling’s role in understanding treatment responses. These findings support further research into immune monitoring for future clinical trials.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1516793/fullsoft tissue sarcomatrabectedinimmunophenotypinggene expression profilingsoluble factorsimmune checkpoints |
| spellingShingle | Paulo Rodrigues-Santos Paulo Rodrigues-Santos Paulo Rodrigues-Santos Paulo Rodrigues-Santos Paulo Rodrigues-Santos Paulo Rodrigues-Santos Jani Sofia Almeida Jani Sofia Almeida Jani Sofia Almeida Jani Sofia Almeida Jani Sofia Almeida Jani Sofia Almeida Luana Madalena Sousa Luana Madalena Sousa Luana Madalena Sousa Patrícia Couceiro Patrícia Couceiro Patrícia Couceiro Patrícia Couceiro António Martinho Joana Rodrigues Ruben Fonseca Manuel Santos-Rosa Manuel Santos-Rosa Manuel Santos-Rosa Manuel Santos-Rosa Manuel Santos-Rosa Paulo Freitas-Tavares José Manuel Casanova José Manuel Casanova José Manuel Casanova José Manuel Casanova José Manuel Casanova Immune monitoring of trabectedin therapy in refractory soft tissue sarcoma patients - the IMMUNYON study Frontiers in Immunology soft tissue sarcoma trabectedin immunophenotyping gene expression profiling soluble factors immune checkpoints |
| title | Immune monitoring of trabectedin therapy in refractory soft tissue sarcoma patients - the IMMUNYON study |
| title_full | Immune monitoring of trabectedin therapy in refractory soft tissue sarcoma patients - the IMMUNYON study |
| title_fullStr | Immune monitoring of trabectedin therapy in refractory soft tissue sarcoma patients - the IMMUNYON study |
| title_full_unstemmed | Immune monitoring of trabectedin therapy in refractory soft tissue sarcoma patients - the IMMUNYON study |
| title_short | Immune monitoring of trabectedin therapy in refractory soft tissue sarcoma patients - the IMMUNYON study |
| title_sort | immune monitoring of trabectedin therapy in refractory soft tissue sarcoma patients the immunyon study |
| topic | soft tissue sarcoma trabectedin immunophenotyping gene expression profiling soluble factors immune checkpoints |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1516793/full |
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