Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Granegger, B.
Prognostic impact of PD-L1 expression in soft tissue sarcoma microenvironment
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2022. pp. 87
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Smolle Maria Anna
- Szkandera Joanna
- Altmetrics:
- Abstract:
- Introduction: The (de)activation of immune checkpoints such as PD-1 and PD-L1 has a significant impact on the immune response and plays an important role in the tumour microenvironment (TME). The identification of these immune checkpoints as reliable prognostic and therapeutic biomarkers contributes to a better understanding of soft tissue sarcoma (STS), eventually giving rise to novel personalized treatment strategies. The aim of this study is to correlate PD-L1 and PD-1 expression as well as tumour infiltrating lymphocytes (TILs) in the TME with clinical prognostic factors and evaluate their prognostic potential towards local recurrence (LR), distant metastasis (DM) and overall survival (OS) in patients with STS. Patients and Methods: In this retrospective analysis, 192 tumour samples were stained and analysed with multispectral imaging. Using multiplex immunohisto-chemistry infiltration rates of TIL phenotypes were assessed: T cells (CD3+), helper T cells (CD3+/CD4+), cytotoxic T cells (CD3+/CD8+), Tregs (CD3+/CD4+/ FOXP3+) and cells positive for PD-1, PD-L1, and FOXP3. The abundance of TIL phenotypes and immune checkpoints were correlated with risk of LR and DM as well as OS. Results: The most abundant biomarker was FOXP3 (2.6% of total cell count) followed by PD-L1 (0.82%) and PD-1 (0.57%). In patients ≥ 63.5 years significantly higher levels of all PD-1+ TIL phenotypes - except for Tregs - were found compared to younger patients. According to histological subtype all TIL phenotypes - except for PD-L1+ T cells - showed significantly higher levels in myxofibrosarcoma (MFS) compared to synovial sarcoma (SS), liposarcoma (LPS), and leiomyosarcoma (LMS). A strong positive correlation between high levels of PD-1+ cells and FOXP3+ cells (rho=0.737) was found. High infiltration rates of Tregs were significantly associated with increased risk for LR (p=0.016). Furthermore, high levels of PD-L1+ cells (p=0.248) and PD-1+ cells (p=0.070) showed a trend towards increased risk for LR, however, not reaching statistical significance. Conclusion: MFS have shown the highest infiltration rates of TILs and immune checkpoint positive cells. High levels of Tregs were significantly associated with increased risk for LR, independent of resection margins.