Summary

Background: Soft tissue sarcoma (STS) is a large and heterogeneous group of malignant mesenchymal neoplasms characterized by a strong tendency toward local recurrence and metastatic spreading. Consistently, the immune microenvironment in sarcomas is highly variable. A new class of material with high electron density, hafnium oxide, was designed at the nanoscale to efficiently absorb ionizing radiation from within the tumor cells and augment the dose deposited to a tumor. […]

Material and Methods: Tumor tissues pre- (biopsy) and post-treatment (resection) are collected from patients with locally advanced STS (NCT02379845), who received either HfO2-NP activated by RT or RT alone. Immunohistochemistry and Digital Pathology for immune biomarkers and Pan-Immune gene expression profiling are analyzed.

Results: A significant increase of CD8+ T cells and a marked increase of CD3+ and PD-1 T cells and CD103+ immune cell infiltration post- vs pre-treatment are observed for HfO2-NP + RT while not differences are seen for RT alone (more than 10 patients analyzed in each arm). Functional analysis of genes expression up-regulated in HfO2-NP + RT post- vs pre-treatment shows an enrichment of cytokine activity (IL7, IFNA, IL11, IFNG), adaptive immunity (RAG1, TAP1, TAP2, TBX21, IFNG, LTK, CD37, CD22) and T cell receptor signaling pathway (CD28, CTLA4, CD274, BTLA, TIGIT, CD5, ZAP70) when compared to RT.

Conclusions: Promising results are observed in patients who received HfO2-NP + RT in terms of immune cells infiltration post- vs pre-treatment when compared to RT. […]