The expression changes of PD-L1 and immune response mediators are related to the severity of primary bone tumors

Author:

Eghtedari Amir Reza,Vaezi Mohammad Amin,Safari Elaheh,Salimi Vahid,Safizadeh Banafsheh,Babaheidarian Pegah,Abiri Amene,Mahdinia Elmira,Alireza Mirzaei ,Mokhles Parisa,Tavakoli-Yaraki MasoumehORCID

Abstract

AbstractThe expression pattern, diagnostic value, and association of PD-L1, IFN-γ and TGF-β with bone tumor type, severity, and relapse are determined in this study. 300 human samples from patients with osteosarcoma, Ewing sarcoma, and GCT were enrolled. The PD-L1 gene and protein expression were assessed by qRT-PCR and immunohistochemistry, respectively. ELISA and flow cytometry was used to detect cytokines and CD4/CD8 T cell percentages, respectively. A considerable increase in PD-L1 level was detected in bone tumor tissues at both gene and protein levels that was considerable in osteosarcoma and Ewing sarcoma. A positive correlation was detected regarding the PD-L1 and tumor metastasis and recurrence in osteosarcoma and Ewing sarcoma. The increased IFN-γ level was detected in patients with metastatic, and recurrent osteosarcoma tumors that were in accordance with the level of TGF-β in these samples. The simultaneous elevation of IFN-γ and TGF-β was detected in Ewing sarcoma and GCT, also the CD4 + /CD8 + ratio was decreased significantly in patients with osteosarcoma compared to GCT tumors. The elevated levels of PD-L1, TGF- β, and IFN-γ were associated with bone tumor severity that can provide insights into the possible role of this axis in promoting immune system escape, suppression, and tumor invasion.

Funder

Iran University of Medical Sciences

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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