Innate immunity in osteosarcoma

Abstract

High-grade osteosarcoma is a malignant bone tumor with the highest incidence in young patients. In chapter 2, we studied MSCs of osteosarcoma patients and found downregulation of HCLS1 in osteosarcoma patient derived MSCs as compared to healthy donor derived MSCs. Despite almost two years in culture, none of the samples underwent spontaneous transformation. An increase in binucleation was noted upon increasing passage in both osteosarcoma patient and healthy donor derived MSCs. In chapter 3, prognostic factors related to the survival of patients with pulmonary metastasized high-grade osteosarcoma were studied. Higher metastatic tumor burden (i.e. larger number of pulmonary nodules), presence of vital metastases upon resection and male sex were associated with an increased risk of death. In chapter 4 we show that osteosarcoma metastasis seems to be inhibited by the presence of macrophages in the tumor microenvironm ent. In chapters 5 and 6 we show that osteosarcoma cells are sensitive to lysis by both autologous and allogeneic NK cells. Patient derived NK cells can be adequately activated by cytokine treatment with IL-15 (chapter 5) or IFN-_ (chapter 6). Therefore, activation of autologous NK cells (either in vivo or ex vivo) may be efficacious. In conclusion, the activation of innate immune cells such as macrophages and NK cells is a promising new adjuvant treatment strategy to treat patients with high-grade osteosarcoma