Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Goda, M.
Comprehensive analysis of tumor microenvironment to predict clinical outcome in soft tissue sarcoma patients after curative resection
Humanmedizin; [ Diplomarbeit ] Medical University of Graz; 2021. pp. 109
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Smolle Maria Anna
- Szkandera Joanna
- Altmetrics:
- Abstract:
- Introduction: The tumor microenvironment (TME) plays a crucial role in tumor behavior and therapeutic efficacy. However, in soft tissue sarcoma (STS), the influence of TME has not been investigated sufficiently. Thus, this diploma thesis aims to examine the correlation between tumor-infiltrating immune cells (TIIC) and patient outcome. Material and methods: In this retrospective analysis, tissue microarrays of one-hundred-eighty-eight STS-patients were stained with multiplex immunohistochemistry and seven immune cell phenotypes were counted automatically on multispectral images: T-cells (CD3+), helper T-cells (CD3+, CD4+), cytotoxic T-cells (CD3+, CD8+), helper memory T-cells (CD3+, CD4+. CD45RO+), B-cells (CD20+), and macrophages (CD68+). Results: The two most common TIIC were CD68+ macrophages (median percentage [MP] 2.93%) and CD3+ T-cells (MP 2.65%). In the multivariate analysis using a Fine & Gray risk-regression model with death as competing event, a significant positive correlation between CD68+ macrophages infiltration and risk of local recurrence (p-value 0.014) independently of age, resection margins, and presence of B-cells, was found. Moreover, the abundance of macrophages was significantly higher in patients older than the median age of 62.5 years (p-value 0.002), whilst B-cell counts were significantly lower (p-value 0.013) in the older patient cohort. Regarding histological subtypes, overall high counts of TIIC in general, and macrophages in particular, were observed in undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma. Conclusion: The data confirm high levels of CD68+ macrophages in STS as a negative prognostic factor regarding local recurrence. Based on these findings, selected STS patient groups might benefit from macrophage-targeting therapies.