The immune microenvironment of giant cell tumor of bone and its role as an indicator to denosumab administration / 中华骨科杂志

ABSTRACT

Objective:To investigate the alteration of immune microenvironment in giant cell tumor of bone (GCTB) after denosumab treatment from the aspect of immune cellsat single-cell level.Methods:During Nov 2018 and May 2020, fresh tumor excision tissues from GCTB cases were collected and received CyTOF analyses. CyTOF datasets were analyzed and visualized by t-distributed stochastic neighbor embedding (TSNE) method of reduction dimension. The compositions of immune cells in GCTB with or without denosumab treatment were compared. The supernatant of culture medium of ex vivo inoculated primary tumor tissues was harvested to clarify if the culturing supernatant could affect cell growth.Results:A total of 15 primary GCTB cases and three denosumab-treated samples were included in this study and were sent for CyTOF and multicolor FACS assay. GCTB was featured of T-cell and macrophage-like myeloid cell-dominant immune microenvironment. After denosumab treatment, the percentage of T-cells was significantly elevated, while the number of macrophage-like myeloid cells were reduced. Furthermore, the ratio of macrophage-like myeloid cells in total live cells was associated with the treatment period of denosumab. The multinuclear osteoclast like giant cells were characterized by the expression of γδTCR, while most of the intratumoral CD8+ T-cells were activated PD-1+CD69+T-cells. The culturing supernatant of denosumab treatment-free GCTB tissues reinforced cell proliferation in vitro, while this phenomenon was not seen when using denosumab treated tissues.Conclusion:Illustrated the immune cell atlas of GCTB, and preliminarily investigated the potential effects of immune cells on tumor progression in GCTB, providing some theoretical clues for prolonged use of denosumab in unresectable GCTB cases.