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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Smolle, MA; Herbsthofer, L; Granegger, B; Goda, M; Brcic, I; Bergovec, M; Scheipl, S; Prietl, B; Pichler, M; Gerger, A; Rossmann, C; Riedl, J; Tomberger, M; López-García, P; El-Heliebi, A; Leithner, A; Liegl-Atzwanger, B; Szkandera, J.
T-regulatory cells predict clinical outcome in soft tissue sarcoma patients: a clinico-pathological study.
Br J Cancer. 2021; 125(5):717-724 Doi: 10.1038/s41416-021-01456-0 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz

Smolle Maria Anna

Szkandera Joanna

Co-Autor*innen der Med Uni Graz

Bergovec Marko

Brcic Iva

El-Heliebi Amin

Gerger Armin

Leithner Andreas

Liegl-Atzwanger Bernadette

Lopez Garcia Pablo

Pichler Martin

Prietl Barbara

Riedl Jakob

Roßmann Christopher Herbert

Scheipl Susanne

Tomberger Martina

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Abstract:

BACKGROUND: Soft tissue sarcomas (STS) are generally considered non-immunogenic, although specific subtypes respond to immunotherapy. Antitumour response within the tumour microenvironment relies on a balance between inhibitory and activating signals for tumour-infiltrating lymphocytes (TILs). This study analysed TILs and immune checkpoint molecules in STS, and assessed their prognostic impact regarding local recurrence (LR), distant metastasis (DM), and overall survival (OS). METHODS: One-hundred and ninety-two surgically treated STS patients (median age: 63.5 years; 103 males [53.6%]) were retrospectively included. Tissue microarrays were constructed, immunohistochemistry for PD-1, PD-L1, FOXP3, CD3, CD4, and CD8 performed, and staining assessed with multispectral imaging. TIL phenotype abundance and immune checkpoint markers were correlated with clinical and outcome parameters (LR, DM, and OS). RESULTS: Significant differences between histology and all immune checkpoint markers except for FOXP3+ and CD3-PD-L1+ cell subpopulations were found. Higher levels of PD-L1, PD-1, and any TIL phenotype were found in myxofibrosarcoma as compared to leiomyosarcoma (all p < 0.05). The presence of regulatory T cells (Tregs) was associated with increased LR risk (p = 0.006), irrespective of margins. Other TILs or immune checkpoint markers had no significant impact on outcome parameters. CONCLUSIONS: TIL and immune checkpoint marker levels are most abundant in myxofibrosarcoma. High Treg levels are independently associated with increased LR risk, irrespective of margins.

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