Multiparametric immunological-molecular profiling of chondrosarcoma

Chondrosarcoma (ChS) is a rare bone malignancy with heterogeneous behavior, the molecular and immunological background of which remains unknown. There is still no effective systemic treatment for patients with ChS. The aim of this study was both immunological and molecular profiling of ChS in correlation with clinical outcomes to develop a classification of patients who can benefit from targeted therapy and immunotherapy. We performed a multiparametric analysis for 99 patients with ChS (including G1-G3 and dedifferentiated subtypes) based on 20 immune markers and targeted next-generation sequencing of 409 genes. We identified three immunophenotypes: “cold”, “hot”, and “intermediate”, of which the presence of “hot” (HR:3.36, CI:1.12-10.1, p<0.05), as well as the occurrence of IDH1 mutations (HR:3.34, CI:1.56-7.2, p<0.01) predicted worse overall survival of patients with ChS in the multivariate Cox model. This study allowed the selection of a group of patients who could potentially benefit from combined immunotherapy with IDH-mutant inhibitors.