Characterizing the tumor microenvironment at the single-cell level reveals the potential immune evasion mechanism in giant cell tumor of bone

Abstract Giant cell tumor of bone (GCTB) is intermediate, locally aggressive primary bone tumor that usually occur in long bones and typically present as lytic lesions, leading to cortical expansion or destruction with a soft-tissue component. At present, the main treatment of GCTB is surgical curettage and bone cement filling, but the recurrence rate is more than 20%. It is known that tumor recurrence and immune escape are closely related to the microenvironment. We need a deeper understanding of the complex tumor microenvironment, as well as the role of various immune cells in the development of GCTB, in order to achieve a comprehensive treatment of GCTB. In this study, GCTB tissue was isolated in vivo from two patients undergoing surgical GCTB, and tumor tissue and its associated immune cell subtypes were identified by single-cell RNA sequencing. In combination with previous studies, the role of Siglec15 in tumor immunosuppression and osteolytic destruction was determined, and validated with recombinant Siglec15 antibody. The results broaden the understanding of the immune-microenvironment of GCTB, and provide a new insight for reducing the recurrence by adjuvant therapy.