PD-L1 and IDO1 expression and tumor-infiltrating lymphocytes in osteosarcoma patients: comparative study of primary and metastatic lesions

Adult Male 0301 basic medicine Osteosarcoma Adolescent Bone Neoplasms Middle Aged Prognosis B7-H1 Antigen 3. Good health Young Adult 03 medical and health sciences Lymphocytes, Tumor-Infiltrating T-Lymphocyte Subsets Tumor Microenvironment Humans Indoleamine-Pyrrole 2,3,-Dioxygenase Female Child Neoplasm Staging
DOI: 10.1007/s00432-020-03242-6 Publication Date: 2020-05-09T18:04:28Z
ABSTRACT
Programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunosuppressive proteins known to be associated with poor prognosis in various cancers. However, their expression and clinical relevance in osteosarcoma remain unknown. In this study, the relationships of PD-L1 and IDO1 expression with clinicopathological features and prognosis were explored.The expression of PD-L1, IDO1, CD3, CD4, and CD8 in 112 formalin-fixed, paraffin-embedded tumor tissues collected by biopsy or surgical resection from 56 osteosarcoma patients was evaluated immunohistochemically. Moreover, four osteosarcoma cell lines were evaluated for the effects of IFNγ on PD-L1 and IDO1 mRNA expression by real-time reverse-transcription polymerase chain reaction.In pre-neoadjuvant chemotherapy (NAC) primary specimens, 10 cases (17%) showed PD-L1 expression and 12 (21%) showed IDO1 expression. Six of ten cases (60%) with PD-L1 positivity co-expressed IDO1. In post-NAC metastatic lesions, the frequency of immunoexpression of PD-L1 and IDO1 was increased compared with that in pre-NAC specimens. PD-L1 and/or IDO1 expression was not associated with poor prognosis. PD-L1 immunoexpression was significantly associated with the infiltration of CD3+ T cells, CD4+ T cells, and CD8+ T cells; while, IDO1 immunoexpression was significantly associated with the infiltration of CD3+ T cells and CD4+ T cells. In all osteosarcoma cell lines, PD-L1 and IDO1 expression was upregulated by stimulation with IFNγ.Our results suggest that the PD-L1 and IDO1 immune checkpoint inhibitors may provide clinical benefit in osteosarcoma patients with metastatic lesions after conventional chemotherapy.
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