Tumor microenvironment in giant cell tumor of bone: evaluation of PD-L1 expression and SIRPα infiltration after denosumab treatment

Sci Rep. 2021 Jul 20;11(1):14821. doi: 10.1038/s41598-021-94022-w.

Abstract

Giant cell tumor of bone (GCTB) is an intermediate malignant bone tumor that is locally aggressive and rarely metastasizes. Denosumab, which is a receptor activator of nuclear factor kappa B ligand (RANKL) inhibitor, can be used to treat GCTB. We focused on potential immunotherapy for GCTB and investigated the tumor microenvironment of GCTB. Programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) expression and signal-regulatory protein alpha (SIRPα), forkhead box P3 (FOXP3), and cluster of differentiation 8 (CD8) infiltration were assessed by immunohistochemical studies of 137 tumor tissues from 96 patients. Of the naive primary specimens, 28% exhibited PD-L1 expression and 39% exhibited IDO1 expression. There was significantly more SIRPα+, FOXP3+, and CD8+ cell infiltration in PD-L1- and IDO1-positive tumors than in PD-L1- and IDO1-negative tumors. The frequency of PD-L1 expression and SIRPα+ cell infiltration in recurrent lesions treated with denosumab was significantly higher than in primary lesions and recurrent lesions not treated with denosumab. PD-L1 expression and higher SIRPα+ cell infiltration were significantly correlated with shorter recurrence-free survival. PD-L1 and SIRPα immune checkpoint inhibitors may provide clinical benefit in GCTB patients with recurrent lesions after denosumab therapy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Differentiation / metabolism*
  • B7-H1 Antigen / metabolism*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / metabolism
  • Denosumab / administration & dosage*
  • Denosumab / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Giant Cell Tumor of Bone / drug therapy*
  • Giant Cell Tumor of Bone / metabolism
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Male
  • Middle Aged
  • Receptors, Immunologic / metabolism*
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • Young Adult

Substances

  • Antigens, Differentiation
  • B7-H1 Antigen
  • CD274 protein, human
  • IDO1 protein, human
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Receptors, Immunologic
  • SIRPA protein, human
  • Denosumab