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Immunology and Immunotherapy

(P 243) CLINICAL SIGNIFICANCE OF TUMOR-INFILTRATING IMMUNE CELL SUBSETS IN THE RETROPERITONEAL DEDIFFERENTIATED LIPOSARCOMAS AND LEIOMYOSARCOMAS

    Author(s)

  • Iva Benesova, Msc

    PhD student
    Institute of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol
    Prague, Hlavni mesto Praha, Czech Republic

    • Co-Author(s)

  • AS

    Antonia Stammberger, MSc

    PhD student
    Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
    Dresden, Sachsen, Germany

  • JB

    Jan Balko, MD, PhD

    Pathologist
    Department of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
    Prague, Hlavni mesto Praha, Czech Republic

  • JP

    Jessica Pablik, MD, PhD

    Pathologist
    Department of Pathology, University Hospital Carl Gustav Carus, Dresden, Germany
    Dresden, Sachsen, Germany

  • AO

    Andrej Ozaniak, MD, PhD

    Surgeon
    Third Department of Surgery, 1st Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
    Prague, Hlavni mesto Praha, Czech Republic

  • LR

    Luise Rupp, MSc, PhD

    Researcher
    Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
    Dresden, Sachsen, Germany

  • RL

    Robert Lischke, Prof., MD

    Head of the Department of Surgery
    Third Department of Surgery, 1st Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
    Prague, Hlavni mesto Praha, Czech Republic

  • JB

    Jirina Bartunkova, Prof., MD

    Head of the Department of Immunology
    Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
    Prague, Hlavni mesto Praha, Czech Republic

  • RW

    Rebekka Wehner, MSc, PhD

    Researcher
    Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany,National Center for Tumor Diseases (NCT), Dresden, Germany, German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany
    Dresden, Sachsen, Germany

  • ZO

    Zuzana Ozaniak Strizova, Assoc. Prof., MD

    Principal investigator
    Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
    Prague, Hlavni mesto Praha, Czech Republic

  • MS

    Marc Schmitz, Prof., MD

    Principal investigator
    Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany,National Center for Tumor Diseases (NCT), Dresden, Germany, German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany
    Dresden, Sachsen, Germany

Objective: Tumor-infiltrating immune cells play a fundamental role in shaping patient prognosis and therapeutic response across many cancers. A deeper understanding of the immune architecture in retroperitoneal dedifferentiated liposarcomas (DDLPS) and leiomyosarcomas (LMS) is warranted to identify novel predictive biomarkers and immunotherapeutic targets.

Methods: To gain novel insights into the immune landscape of retroperitoneal DDLPS and LMS, we explored the spatial organization, frequency, and proportions of CD8+ T cell (including activated, proliferating, and exhausted phenotypes), CD4+ T cell, and macrophage subsets in primary treatment-naïve retroperitoneal DDLPS (n = 22) and LMS tissues (n = 10) using multiplex immunohistochemistry. Immune cell distribution was assessed in the tumor area and invasive margin. These results were subsequently correlated with clinicopathological characteristics of the patients.

Results: When investigating the whole cohort, CD8+LAG-3+ T cells comprised the highest proportion of all analyzed CD8+ subsets. Their elevated density was associated with improved overall survival (OS). High proportions of CD8+LAG-3+ T cells emerged as an independent prognostic factor for OS. Moreover, proliferating CD8+ subsets demonstrated clinical relevance. High proportions of CD8+Ki-67+LAG-3+ T cells were linked to significantly prolonged metastasis-free survival (MFS), while both the density and proportion of CD8+Ki-67+PD-1+ T cells were independent prognostic factors for progression-free survival (PFS). Interestingly, an enhanced density of regulatory T cells correlated with favorable survival outcomes. The density and proportions of CD4+ and CD8+ subsets did not significantly differ between DDLPS and LMS. Macrophages were the predominant immune cell population within this cohort, and M2-like macrophages (CD68+CD163+) accounted for 40.7% of the macrophage compartment. A lower density of M2-like macrophages was linked to better PFS and recurrence-free survival.

Conclusion: These findings highlight the clinical relevance of immune infiltration in retroperitoneal DDLPS and LMS. They support the rationale for further exploration of the immune architecture for prognostic biomarkers and development of targeted immunotherapeutic strategies to improve the clinical outcomes of these patients.

Funding: AZV NU23J-08–00031, GA UK 94323