Immunotherapeutic strategies for the treatment of chondrosarcoma and the impact of resections around the shoulder

Chondrosarcoma is the second most common primary bone malignancy. The clinical behavior of these tumors is closely related to their histological grading. Especially high-grade conventional and dedifferentiated chondrosarcoma are aggressive tumors with a poor prognosis. Therefore, there is a need for more effective therapies.
In this thesis we explored different immunotherapeutic strategies in chondrosarcoma. We showed that chondrosarcoma are immunogenic tumors as indicated by the tumor infiltrating lymphocytes. The defects in HLA class I antigen and the expression of the checkpoint molecules B7-H3 and PD-1/PD-L1 indicate that chondrosarcoma tumor cells utilize escape mechanisms to avoid immune recognition and subsequent destruction.
These results contribute to the rational design of immunotherapeutic strategies for the treatment of chondrosarcoma, such as systemic therapies targeting B7-H3 and PD-1/PD-L1.
We also showed CSPG4, as a promoter of disease, in chondrosarcoma and therefore as a clinically relevant target. This provides a rationale for future studies to investigate the effectiveness of CSPG4 directed therapy, such a CSPG4-targeted CAR T cell immunotherapy, in vivo.
Further we investigated the impact of oncological resections of the shoulder since this is one of the most common locations for chondrosarcoma. Endoprostheses, osteoarticular allografts, and allograft-prosthesis composites seem largely comparable in functional outcome and implant survival, where overall complications seems higher in the osteoarticular allograft group based on higher fracture rates. Patients treated with oncological resection of the scapula and/or clavicle have a considerable good upper extremity function that was predicated on preservation of the glenoid and rotator cuff.