Increased PD-L1 and T-cell infiltration in the presence of HLA class I expression in metastatic high-grade osteosarcoma: a rationale for T-cell-based immunotherapy.

Abstract

INTRODUCTION:

Immunotherapy may be an excellent choice for treating osteosarcoma given its exceptionally high genomic instability, potentially generating neoantigens. In this study, we aim to investigate the HLA class I expression, PD-L1 and tumour-infiltrating lymphocytes in primary osteosarcomas and relapses/metastases, as well as their changes during disease progression.

MATERIALS AND METHODS:

Tumour samples from multiple stages of the disease (pretreatment biopsies, surgical resections of primary osteosarcomas, relapses and metastases) were collected and stained for HLA-A (HCA2), HLA-B/C (HC10), β2-microglobulin and PD-L1 using immunohistochemistry on whole sections. Density and type of T-cell infiltrate were characterised by a triple immunofluorescent staining CD3-CD8-FOXP3.

RESULTS:

Overall, 85 formalin-fixed, paraffin-embedded blocks from 25 osteosarcoma patients were included. HLA class I expression was detected in 94% of osteosarcomas (strongly positive in 56%, heterogeneous in 38%) and negative or weakly positive in 6%, without differences between the stages of the disease. HLA-A expression was more frequently negative than HLA-B/C. Tumour-infiltrating lymphocytes were highly heterogeneous and mainly observed in tumour areas with expression of HLA class I. Density of T cells was significantly higher in metastases than in primary tumours and local relapses (p = 0.0003). Positive PD-L1 expression was found in 13% of primary tumours, 25% of relapses and 48% of metastases and correlated with a high T-cell infiltrate (p = 0.002).

CONCLUSION:

An increased number of tumour-infiltrating T cells and PD-L1 expression in metastases compared with primary tumours, suggesting accessibility for T cells, could imply that osteosarcoma patients with metastatic disease may benefit from T-cell-based immunotherapy.

• Authors: Yayan T Sundara, Marie Kostine, Arjen H G Cleven, Judith V M G Bovée, Marco W Schilham, Anne-Marie Cleton-Jansen
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 66 Issue 1 Pg. 119-128 (01 2017) ISSN: 1432-0851 [Electronic] Germany
• PMID: 27853827 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human
• Histocompatibility Antigens Class I

Topics

• Adolescent
• Adult
• Aged
• B7-H1 Antigen (biosynthesis, immunology)
• Biomarkers, Tumor (immunology)
• Bone Neoplasms (immunology, therapy)
• Child
• Female
• Histocompatibility Antigens Class I (immunology)
• Humans
• Immunotherapy (methods)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Male
• Middle Aged
• Neoplasm Metastasis
• Osteosarcoma (immunology, therapy)
• Prognosis
• Young Adult