PD-L1 and IDO1 expression and tumor-infiltrating lymphocytes in osteosarcoma patients: comparative study of primary and metastatic lesions
PD-L1 and IDO1 expression and tumor-infiltrating lymphocytes in osteosarcoma patients: comparative study of primary and metastatic lesions
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DOI：
10.1007/s00432-020-03242-6
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发表时间：
2020-05-09
影响因子：
3.6
通讯作者：
Oda, Yoshinao
中科院分区：
文献类型：
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作者：
Toda, Yu;Kohashi, Kenichi;Oda, Yoshinao
目的程序性死亡配体1（PD-L1）和吲哚胺2，3-双加氧酶1（IDO 1）是免疫抑制蛋白，已知与多种癌症的不良预后相关。然而，它们在骨肉瘤中的表达和临床意义仍然未知。本研究探讨PD-L1和IDO 1表达与乳腺癌临床病理特征及预后的关系。方法采用免疫组化方法检测56例骨肉瘤患者手术切除或活检的112例骨肉瘤组织中PD-L1、IDO 1、CD 3、CD 4和CD 8的表达。此外，通过实时逆转录聚合酶链反应评价了4种骨肉瘤细胞系IFN γ对PD-L1和IDO 1 mRNA表达的影响。结果在新辅助化疗（NAC）前原发灶标本中，10例（17%）PD-L1阳性，12例（21%）IDO 1阳性。10例PD-L1阳性病例中有6例（60%）共表达IDO 1。在NAC后转移灶中，PD-L1和IDO 1的免疫表达频率与NAC前标本相比增加。PD-L1和/或IDO 1表达与不良预后无关。PD-L1免疫表达与CD 3（+）T细胞、CD 4（+）T细胞和CD 8（+）T细胞浸润显著相关;而IDO 1免疫表达与CD 3（+）T细胞和CD 4（+）T细胞浸润显著相关。在所有的骨肉瘤细胞系中，PD-L1和IDO 1的表达通过IFN γ刺激而上调。结论PD-L1和IDO 1免疫检查点抑制剂对骨肉瘤常规化疗后出现转移灶的患者有较好的临床疗效。
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 IFN gamma 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 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 IFN gamma. 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.