Analysis of PD-L1, T-cell infiltrate and HLA expression in chondrosarcoma indicates potential for response to immunotherapy specifically in the dedifferentiated subtype.
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.
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.|Department of Rheumatology, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux Cedex, France.
Marie
M
Kostine
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Arjen Hg
AH
Cleven
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Noel F C C
NF
de Miranda
Department of Medical Oncology, Institut Bergonié, Bordeaux Cedex, France.
Antoine
A
Italiano
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Anne-Marie
AM
Cleton-Jansen
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Judith V M G
JV
Bovée
D060890:B7-H1 Antigen / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D054337:Cell Dedifferentiation; D002813:Chondrosarcoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D005060:Europe; D006680:HLA Antigens / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D058990:Molecular Targeted Therapy; D018579:Patient Selection; D013601:T-Lymphocytes / Q000276:immunology*; D046888:Tissue Array Analysis
D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D006680:HLA Antigens