Analysis of PD-L1, T-cell infiltrate and HLA expression in chondrosarcoma indicates potential for response to immunotherapy specifically in the dedifferentiated subtype.
Mod Pathol
; 29(9): 1028-37, 2016 09.
Article
em En
| MEDLINE
| ID: mdl-27312065
ABSTRACT
Therapies targeting the programmed cell death 1 (PD-1) or its ligand (PD-L1) promote antitumor T-cell activity, leading to unprecedented long-lasting tumor responses in some advanced cancers. Because of radiotherapy and chemotherapy resistance, no effective treatments have been defined for advanced chondrosarcomas. We here report an immunohistochemical analysis of PD-L1 expression in a large series of conventional, mesenchymal, clear cell and dedifferentiated chondrosarcomas using tissue microarrays. In the PD-L1-positive tumors, we analyzed the immune microenvironment (T-cell and macrophage infiltration as well as HLA class I expression) using whole sections. PD-L1 expression was absent in conventional (n=119), mesenchymal (n=19) and clear cell (n=20) chondrosarcomas. Forty-one percent (9 of the 22) of dedifferentiated chondrosarcomas displayed PD-L1 positivity. These results were confirmed in an independent cohort using whole tissue sections of dedifferentiated chondrosarcomas in which PD-L1 expression was detected in 52% (11 of the 21) of cases. PD-L1 expression was exclusively found in the dedifferentiated component and expression positively correlated with other immune parameters such as high number of tumor-infiltrating lymphocytes (P=0.014) and positive HLA class I expression (P=0.024) but not with patient overall survival (P=0.22). The presence of PD-L1 expression in association with immune-infiltrating cells and HLA class I expression in nearly 50% of the dedifferentiated chondrosarcomas provides rationale for including these patients in clinical trials with PD-1/PD-L1-targeted therapies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ósseas
/
Linfócitos T
/
Biomarcadores Tumorais
/
Condrossarcoma
/
Linfócitos do Interstício Tumoral
/
Desdiferenciação Celular
/
Antígeno B7-H1
/
Antígenos HLA
Tipo de estudo:
Clinical_trials
Limite:
Humans
País/Região como assunto:
Europa
Idioma:
En
Revista:
Mod Pathol
Assunto da revista:
PATOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Holanda