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Published on: March 22, 2024
Together Intra-Tumor Hypoxia and Macrophagic Immunity Are Driven Worst Outcome in Pediatric High-Grade Osteosarcomas
Charlotte Nazon1, Marina Pierrevelcin2, Thibault Willaume3
1Pediatric Onco-Hematology Unit, University Hospital of Strasbourg, 1 Avenue Molière, CEDEX, 67098 Strasbourg, France.
Background:
Osteosarcomas (OTS) represent the most common primary bone cancer diagnosed in adolescents and young adults. Despite remarkable advances, there are no objective molecular or imaging markers able to predict an OTS outcome at diagnosis. Focusing on biomarkers contributing broadly to treatment resistance, we examine the interplay between the tumor-associated macrophages and intra-tumor hypoxia.
Methods:
Radiological and immunohistochemical (IHC) data were correlated with the outcome in a retrospective and monocentric cohort of 30 pediatric OTS. We studied hypoxic (pS6, phospho-mTor, HIF-1α and carbonic anhydrase IX (CAIX)) and macrophagic (CD68 and CD163) biomarkers.
Results:
The imaging analyses were based on MRI manual volumetric measures on axial post-contrast T1 weighted images, where, for each tumor, we determined the necrotic volume and its ratio to the entire tumor volume. When they were above 50 cm3 and 20%, respectively, they correlated with a worse overall survival (p = 0.0072 and p = 0.0136, respectively) and event-free survival (p = 0.0059 and p = 0.0143, respectively). IHC assessments enable a significant statistical link between HIF-1α/CAIX hyper-expressions, CD68+ cells and a worse outcome, whereas activation of mTor pathway was linked to a better survival rate and CD163+ cells.
Conclusions:
This study evidenced the links between hypoxia and immunity in OTS, as their poor outcome may be related to a larger necrotic volume on diagnostic MRI and, in biopsies, to a specific IHC profile.
Insights
Larger necrotic tumor volume on diagnostic MRI and specific IHC profiles in osteosarcomas (OTS) correlate with poor outcomes. Hypoxia and immune cell markers (HIF-1α/CAIX, CD68) indicate worse survival in pediatric OTS.
Area of Science:
- Oncology
- Radiology
- Immunology
Background:
- Osteosarcomas (OTS) are the most common primary bone cancer in young people.
- Current treatments lack reliable biomarkers for predicting patient outcomes.
- Tumor-associated macrophages and hypoxia are implicated in treatment resistance.
Purpose of the Study:
- To investigate the relationship between tumor hypoxia, macrophages, and treatment outcomes in pediatric osteosarcomas.
- To identify potential imaging and molecular biomarkers for predicting osteosarcoma prognosis.
Main Methods:
- Retrospective analysis of radiological and immunohistochemical (IHC) data from 30 pediatric osteosarcoma patients.
- Assessed hypoxic markers (HIF-1α, CAIX) and macrophagic markers (CD68, CD163) via IHC.
- Correlated MRI-derived necrotic tumor volume with patient survival outcomes.
Main Results:
- Larger necrotic tumor volume (>50 cm³ or >20% ratio) on diagnostic MRI significantly correlated with worse overall and event-free survival.
- High expression of HIF-1α and CAIX, along with increased CD68+ cells, was linked to poorer outcomes.
- Activation of the mTor pathway and CD163+ cells were associated with better survival rates.
Conclusions:
- Diagnostic MRI necrotic volume and specific IHC profiles (hypoxia and immune markers) are valuable indicators of osteosarcoma prognosis.
- The interplay between tumor hypoxia and the immune microenvironment significantly influences osteosarcoma outcomes.
- This study highlights potential biomarkers for improved patient stratification and treatment strategies in osteosarcoma.
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