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

• DOI: 10.1007/s00262-016-1925-3
• Publication Date: 2016-11-17T01:55:30Z
• Authors: Yayan T. Sundara; Marie Kostine; Arjen H. G. Cleven; Judith V. M. G. B...; Marco W. Schilham; Anne-Marie Cleton...
• Keywords: PD-L1; Adult; Male; 0301 basic medicine; Cancer Research; Adolescent; Immunology; Bone Neoplasms; B7-H1 Antigen; Young Adult; 03 medical and health sciences; Lymphocytes, Tumor-Infiltrating; 0302 clinical medicine; Biomarkers, Tumor; Immunology and Allergy; Humans; Neoplasm Metastasis; Child; Aged; Osteosarcoma; Tumour-infiltrating lymphocytes; Histocompatibility Antigens Class I; HLA class I; Middle Aged; Prognosis; 3. Good health; Oncology; Original Article; Female; Immunotherapy

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 relapses/metastases, as well their changes during disease progression. Tumour samples from multiple stages of (pretreatment biopsies, surgical resections osteosarcomas, relapses metastases) were collected stained HLA-A (HCA2), HLA-B/C (HC10), β2-microglobulin using immunohistochemistry on whole sections. Density type T-cell infiltrate characterised by a triple immunofluorescent staining CD3-CD8-FOXP3. Overall, 85 formalin-fixed, paraffin-embedded blocks 25 patients included. expression was detected 94% (strongly positive 56%, heterogeneous 38%) negative or weakly 6%, without differences between disease. more frequently than HLA-B/C. Tumour-infiltrating highly mainly observed tumour areas with I. T cells significantly higher metastases tumours local (p = 0.0003). Positive found 13% tumours, 25% 48% correlated 0.002). An increased number compared suggesting accessibility cells, could imply that metastatic benefit T-cell-based immunotherapy.