PD-L1 and IDO1 expression and tumor-infiltrating lymphocytes in osteosarcoma patients: comparative study of primary and
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ORIGINAL ARTICLE – CLINICAL ONCOLOGY
PD‑L1 and IDO1 expression and tumor‑infiltrating lymphocytes in osteosarcoma patients: comparative study of primary and metastatic lesions Yu Toda1 · Kenichi Kohashi1 · Yuichi Yamada1 · Masato Yoshimoto1 · Shin Ishihara1 · Yoshihiro Ito1 · Takeshi Iwasaki1 · Hidetaka Yamamoto1 · Yoshihiro Matsumoto2 · Yasuharu Nakashima2 · Masaaki Mawatari3 · Yoshinao Oda1 Received: 17 February 2020 / Accepted: 1 May 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose 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. Methods 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. Results 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 C D3+ T cells, C D4+ T cells, and C D8+ 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. Conclusion 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. Keywords PD-L1 · IDO1 · Osteosarcoma · Tumor-infiltrating lymphocyte · Metastatic lesion
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00432-020-03242-6) contains supplementary material, which is available to authorized users. * Yoshinao Oda [email protected]‑u.ac.jp 1
Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Maidashi 3‑1‑1, Higashi‑ku, Fukuoka 812‑8582, Japan
2
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
3
Department of Orthopaedic Surgery, Faculty of Medicine, Saga University, Saga, Japan
Abbreviations PD-L1 Programmed death ligand 1 IDO1 Indoleamine 2,3-dioxygenase 1 NAC Neoadjuvant chemo
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