Abstract

Abstract Background and purpose: Giant cell tumor of bone (GCTB) is a locally aggressive tumor with metastatic potential. Given that GCTBs are composed of three major cell populations and the bone-resorption activity is attributed to the multinucleated giant cells which are conjectured to be recruited by “real” tumor cells, it is still elusive that how and what are these immune cells recruited. The purpose of this study is to present the immune landscape of GCTB, as well as to find out responsible chemokines during immune cell recruiting. Experimental procedures: We collected fresh GCTB tissues from surgical excisions. To identify immune cell composition within the tumor microenvironment, we performed mass cytometry (CyTOF) and conventional multicolor cytometry. Some fresh osteosarcoma and chondrosarcoma samples were also used to compare the immune atlas. For chemokine profiling, chemokine arrays were utilized. Further analysis on potential association between chemokines and immune cells were conducted. Results: For last updated, 47 GCTB fresh samples were collected, of which 12 cases received CyTOF analysis and the rest 35 samples were analyzed by multicolor cytometry. All GCTB samples were analyzed by chemokine array In-depth interrogation of the immune landscapes showed that compared with osteosarcoma and chondrosarcoma, GCTBs had some unique immune cell subgroups. Some CD163+ CD206+ macrophage clusters which expressed various immune suppressive markers were significantly enriched in GCTBs, while CD4+ CD25+ Treg cells were fewer in GCTB. In addition, some macrophage-like mononuclear cells (CD14- CD68+ CD163- CD206+ HLA-DR+) were only seen in GCTBs.Chemokine array revealed that higher levels of CXCL12, CCL22, and CCL7 might be associated with moremacrophage-like mononuclear cells in GCTBs. Conclusion: GCTB have very different immune features from other malignant bone tumors. Multiple chemokines may play important roles in recruiting “functional” monocytes. Such in-depth understanding has important implications in appropriate therapeutics for GCTB. Bigger sample size will further help in studying the immune and chemokine features of GCTB. Note: This abstract was not presented at the meeting. Citation Format: Binghao Li, Zhan Wang, Zhaoming Ye. The immune atlas and chemokine profile of giant cell tumor of bone [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1486.

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