Clinical outcome of osteosarcoma and its correlation with programmed death-ligand 1 and T cell activation markers

• Main Authors: Yoshida K, Okamoto M, Sasaki J, Kuroda C, Ishida H, Ueda K, Okano S, Ideta H, Kamanaka T, Sobajima A, Takizawa T, Kito M, Aoki K, Uemura T, Haniu H, Kato H, Saito N
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-04-01
• Series: OncoTargets and Therapy
• Subjects: anti-PD-1 antibody; perforin; granzyme B; IFNγ; osteosarcoma; clinical outcome
• Online Access: https://www.dovepress.com/clinical-outcome-of-osteosarcoma-and-its-correlation-with-programmed-d-peer-reviewed-article-OTT

Kazushige Yoshida,1 Masanori Okamoto,1 Jun Sasaki,1 Chika Kuroda,2 Haruka Ishida,2 Katsuya Ueda,2 Satomi Okano,2 Hirokazu Ideta,1 Takayuki Kamanaka,1 Atsushi Sobajima,1 Takashi Takizawa,1 Munehisa Kito,1 Kaoru Aoki,3 Takeshi Uemura,2 Hisao Haniu,2 Hiroyuki Kato,1 Naoto Saito2 1Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan; 2Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, Japan; 3Physical Therapy Division, School of Health Sciences, Shinshu University School of Medicine, Matsumoto, Japan Purpose: Although both anti-PD-1 antibody and treatments using anti-PD-L1 antibody are currently in clinical use, their therapeutic effects vary according to cancer type. One of the factors accounting for this variability is the expression level of the immune checkpoint molecule that differs between cancer types; thus, it is important to clarify the relationship between clinical outcomes and immune checkpoint molecules for all types of human cancer. The purpose of this study is to evaluate the clinical outcome of osteosarcoma in relation to PD-L1, PRF, GZMB, and IFNγ expression. Methods: Using 19 clinical specimens of osteosarcoma, we examined the expression of PD-L1, PRF, GZMB, and IFNγ in relation to their clinical outcomes. Results: PD-L1 expression correlated with early metastatic formation in clinical specimens of osteosarcoma, and the group with highly expressed functional markers for T cells such as PRF and GZMB resulted in a long overall survival time. Conclusion: This is the first study to elucidate the clinical outcomes of osteosarcoma in relation to PD-L1, PRF, GZMB, and IFNγ expression. This study provides valuable information regarding the clinical indication and prediction of effect for anti-PD-1 antibody in osteosarcoma. Keywords: anti-PD-1 antibody, perforin, granzyme B, IFNγ, osteosarcoma, clinical outcome