Abstract 97P
Background
Chondrosarcoma, or malignant cartilage tumor, is the second most common bone cancer after osteosarcoma. Chemo- and radio-resistant due to its poor vascularization and the chondrogenic nature of its extracellular matrix (ECM), its management relies mainly on surgery, underlining the limited therapeutic arsenal. In addition to its unique appearance, this tumor is characterized by a microenvironment rich in immune cells such as lymphocytes and tumor-associated macrophages (TAMs). TAMs are the most common cell population in these tumors, and can represent more than 50% of tumor mass. Most of these cells, known as M2-like TAMs since they display the characteristics of M2 macrophages, have pro-tumoral properties and participate in various processes such as invasion and chemoresistance. Due to the rarity of this pathology, few data are available on cancer cell/TAM interactions, highlighting the need to develop models to study these interactions and evaluate therapeutic strategies involving the macrophagic component such as mifamurtide, an immunostimulator. In this context, UMR 1240 Inserm/UCA IMoST, drawing on its expertise in chondrosarcoma, has developed an innovative cocultured tumoroid model between grade 3 chondrosarcoma cells (CH2879) and immortalized human monocytes (THP-1).
Methods
This new in vitro model was characterized and compared to the in vivo xenograft model and then used to assess treatment effect. After demonstrating the ability of cancer cells to recruit monocytes, tumoroid microenvironment was characterized.
Results
Interestingly, as the in vivo preclinical model, the tumoroid is characterized by the presence of M2-like TAMs in the periphery, correlating with increased accumulation of MMP-9 and COX-2 (enzymes involved in ECM remodeling and invasion). In addition, the cocultured tumoroid showed chemoresistance to doxorubicin with IC50 two times higher compared to the monoculture model. Finally, Mifamurtide treatment is currently being evaluated, suggesting a potential effect.
Conclusions
Taken together, these results point to the development of a relevant preclinical model mimicking cell/matrix and cell/cell interactions that can be used to evaluate new treatments, with the aim of improving the management of this orphan pathology.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
UMR 1240 INSERM UCA.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.