Basic StudiesCheckpoint Blockade in Combination With Doxorubicin Augments Tumor Cell Apoptosis in OsteosarcomaWang, Jizhuang*,†; Hu, Chuanzhen*,†; Wang, Jun†; Shen, Yuhui*,†; Bao, Qiyuan*; He, Fangzhou*; Wang, Hongyi*,†; Gong, Liangzhi*,†; Liu, Zhuochao*,†; Hu, Fangqiong†; Liang, Jing†; Zhou, Qi†; Wei, Li†; Wen, Junxiang*,†; Zhang, Weibin*,†Author Information *Department of Orthopaedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine †Shanghai Key Laboratory for Prevention and treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Orthopedics and Traumatology, Shanghai, People’s Republic of China Jizhuang Wang, C.H., and Jun Wang: contributed equally. Reprints: Junxiang Wen and Weibin Zhang, Department of Orthopaedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijiner Road, Shanghai 200025, People’s Republic of China (e-mails: email@example.com; firstname.lastname@example.org). Journal of Immunotherapy: November/December 2019 - Volume 42 - Issue 9 - p 321-330 doi: 10.1097/CJI.0000000000000281 Buy Metrics Abstract The aim of this study was to provide a basis for the theory that the combination of conventional chemotherapy and immunotherapy would be an effective treatment for osteosarcoma. Here, the expression of programmed death ligand 1 (PD-L1) in 26 clinical osteosarcoma tissue samples collected before and after chemotherapy was analyzed. The effects of osteosarcoma cells treated with doxorubicin, a conventional chemotherapeutic agent, on the proliferation and apoptosis of CD8+ T lymphocytes were investigated in vitro. Thereafter, the effectiveness of doxorubicin combined with an anti-PD-L1 antibody as an osteosarcoma therapy was tested in 24 subcutaneous tumor mouse models. The results showed that the expression of PD-L1 was upregulated by chemotherapy in both the clinical osteosarcoma tissue samples and the osteosarcoma cell lines. The proliferation of CD8+ T lymphocytes was inhibited, and apoptosis in CD8+ T lymphocytes was enhanced by the doxorubicin-pretreated osteosarcoma cells, whereas this effect was reversed by the anti-PD-L1 antibody. A more effective result was observed when doxorubicin was combined with the anti-PD-L1 antibody in vivo. In short, the combination of conventional chemotherapy and an anti-PD-L1 antibody might be an effective option for osteosarcoma treatment, as anti-PD-L1 antibody can reverse the immunosuppression induced by chemotherapy. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.