(P 369) MAGEA ANTIGENS AS IMMUNOTHERAPEUTIC TARGETS FOR ADVANCED OSTEOSARCOMA

Objective: Osteosarcoma is the most common primary bone sarcoma. About 50% of patients develop metastatic disease and their 5-year survival lingers at around 20-30%. T cell checkpoint blockade immunotherapies have revolutionized cancer treatment in the last decade, but their impact remains limited in osteosarcoma. Therefore, we aimed to identify novel immunotherapeutic targets for osteosarcoma patients with advanced disease by exploring the immunological changes that accompany osteosarcoma progression.

Methods: We performed immunogenic characterization of a unique sample set containing multiple osteosarcoma samples of seven patients, collected during the course of disease. These included primary biopsies (n=5), primary resections (n=6), local recurrences (n=3) and metastases (n=10). For these samples, we performed RNA-sequencing and imaging mass cytometry to reveal the immunological landscape during osteosarcoma progression.

Results: Gene expression analysis of osteosarcoma samples revealed an increased cytotoxic immune signature in osteosarcoma metastases compared to primary tumors, which may result from a coordinated T cell driven anti-tumor immune response. Immunophenotyping with imaging mass cytometry further confirmed the increased T cell infiltrate in metastatic lesions. In parallel, we found a pronounced increase in the expression of cancer testis antigens in osteosarcoma metastases, in particular MAGEA-related antigens. Their overexpression in metastatic lesions was confirmed at protein level and, importantly, we demonstrated the presentation of MAGE-derived peptides in three osteosarcoma cell lines.

Conclusion: We provide evidence for a concomitant increase in cytotoxic anti-tumor immune responses and expression of MAGEA antigens from primary to metastatic osteosarcoma. This observation warrants the exploration of MAGEA antigens as immunotherapeutic targets for the treatment of advanced osteosarcoma.