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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1516793

Immune Monitoring of Trabectedin Therapy in Refractory Soft Tissue Sarcoma Patients -the IMMUNYON Study

Provisionally accepted
Paulo Rodrigues-Santos Paulo Rodrigues-Santos 1*Jani Almeida Jani Almeida 2Luana Sousa Luana Sousa 3Patrícia Couceiro Patrícia Couceiro 3António Martinho António Martinho 4Joana Rodrigues Joana Rodrigues 5Ruben Fonseca Ruben Fonseca 5Manuel Santos-Rosa Manuel Santos-Rosa 2Paulo Freitas Tavares Paulo Freitas Tavares 5José Manuel Casanova José Manuel Casanova 5
  • 1 Instituto de Imunologia, Institute of Immunology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
  • 2 Institute of Immunology, Faculty of Medicine, University of Coimbra, Coimbra, Coimbra, Portugal
  • 3 Immunology and Oncology Laboratory, Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Coimbra, Portugal
  • 4 Blood and Transplantation Center of Coimbra, Portuguese Institute of Blood and Transplantation, Coimbra, Coimbra, Portugal
  • 5 Coimbra Hospital and University Center, Coimbra, Coimbra, Portugal

The final, formatted version of the article will be published soon.

    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.

    Keywords: Soft Tissue Sarcoma, Trabectedin, Immunophenotyping, Gene Expression Profiling, Soluble factors, immune checkpoints, Progression free survival

    Received: 24 Oct 2024; Accepted: 07 Jan 2025.

    Copyright: © 2025 Rodrigues-Santos, Almeida, Sousa, Couceiro, Martinho, Rodrigues, Fonseca, Santos-Rosa, Tavares and Casanova. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Paulo Rodrigues-Santos, Instituto de Imunologia, Institute of Immunology, Faculty of Medicine, University of Coimbra, Coimbra, 3004-504, Portugal

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