TY - JOUR
T1 - Tumor microenvironment in giant cell tumor of bone
T2 - evaluation of PD-L1 expression and SIRPα infiltration after denosumab treatment
AU - Toda, Yu
AU - Kohashi, Kenichi
AU - Yamamoto, Hidetaka
AU - Ishihara, Shin
AU - Ito, Yoshihiro
AU - Susuki, Yosuke
AU - Kawaguchi, Kengo
AU - Kiyozawa, Daisuke
AU - Takamatsu, Dai
AU - Kinoshita, Izumi
AU - Yamada, Yuichi
AU - Maehara, Junki
AU - Kimura, Atsushi
AU - Tamiya, Sadafumi
AU - Taguchi, Kenichi
AU - Matsunobu, Tomoya
AU - Matsumoto, Yoshihiro
AU - Nakashima, Yasuharu
AU - Mawatari, Masaaki
AU - Oda, Yoshinao
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-021-94022-w
DO - 10.1038/s41598-021-94022-w
M3 - Article
C2 - 34285260
AN - SCOPUS:85111143767
VL - 11
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 14821
ER -