Analysis of PD-L1, T-cell infiltrate and HLA expression in chondrosarcoma indicates potential for response to immunotherapy specifically in the dedifferentiated subtype.

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.

• Authors: Marie Kostine, Arjen Hg Cleven, Noel F C C de Miranda, Antoine Italiano, Anne-Marie Cleton-Jansen, Judith V M G Bovée
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 29 Issue 9 Pg. 1028-37 (09 2016) ISSN: 1530-0285 [Electronic] United States
• PMID: 27312065 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human
• HLA Antigens

Topics

• B7-H1 Antigen (analysis)
• Biomarkers, Tumor (analysis)
• Bone Neoplasms (immunology, pathology, therapy)
• Cell Dedifferentiation
• Chondrosarcoma (immunology, pathology, therapy)
• Europe
• HLA Antigens (analysis)
• Humans
• Immunohistochemistry
• Immunotherapy (methods)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Molecular Targeted Therapy
• Patient Selection
• T-Lymphocytes (immunology)
• Tissue Array Analysis