The immune landscape of chondrosarcoma reveals an immunosuppressive environment and exposes macrophages as a promising therapeutic target

Publication date: Available online 26 November 2019Source: Journal of Bone OncologyAuthor(s): Richert Iseulys, Gomez-Brouchet Anne, Bouvier Corinne, Du Bouexic De Pinieux Gonzague, Karanian Marie, Blay Jean-Yves, Dutour AurélieAbstractSurvival rate for Chondrosarcoma (CHS) is at a standstill, more effective treatments are urgently needed. Consequently, a better understanding of CHS biology and its immune environment is crucial to identify new prognostic factors and therapeutic targets.Here, we exhaustively describe the immune landscape of conventional and dedifferentiated CHS. Using IHC and molecular analyses (RT-qPCR), we mapped the expression of immune cell markers (CD3, CD8, CD68, CD163) and immune checkpoints (ICPs) from a cohort of 27 conventional and 49 dedifferentiated CHS. The impact of the density of tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs) and immune checkpoints (ICPs) on clinical outcome were analyzed.We reveal that TAMs are the main immune population in CHS. Focusing on dedifferentiated CHS, we found that immune infiltrate composition is correlated with patient outcome, a high CD68+/CD8+ ratio being an independent poor prognostic factor (p < 0.01), and high CD68+ levels being associated with the presence of metastases at diagnosis (p < 0.05). Among the ICPs evaluated, CSF1R, B7H3, SIRPA, TIM3 and LAG3 were expressed at the mRNA level in both CHS subtypes. Furthermore, CSF1R expression by TAMs was confirmed using IHC in 89...
Source: Journal of Bone Oncology - Category: Cancer & Oncology Source Type: research