Checkpoint Blockade in Combination With Doxorubicin Augments Tumor Cell Apoptosis in Osteosarcoma

التفاصيل البيبلوغرافية
العنوان: Checkpoint Blockade in Combination With Doxorubicin Augments Tumor Cell Apoptosis in Osteosarcoma
المؤلفون: Jun Wang, Chuanzhen Hu, Qi Zhou, Jing Liang, Zhuochao Liu, Junxiang Wen, Fangzhou He, Yuhui Shen, Hongyi Wang, Qiyuan Bao, Liangzhi Gong, Weibin Zhang, Fangqiong Hu, Jizhuang Wang, Li Wei
المصدر: Journal of immunotherapy (Hagerstown, Md. : 1997). 42(9)
سنة النشر: 2019
مصطلحات موضوعية: musculoskeletal diseases, 0301 basic medicine, Cancer Research, medicine.medical_treatment, Immunology, Antineoplastic Agents, Apoptosis, Bone Neoplasms, CD8-Positive T-Lymphocytes, Antibodies, B7-H1 Antigen, 03 medical and health sciences, 0302 clinical medicine, In vivo, Cell Line, Tumor, Antineoplastic Combined Chemotherapy Protocols, medicine, Immunology and Allergy, Animals, Humans, Doxorubicin, neoplasms, Cell Proliferation, Pharmacology, Chemotherapy, Mice, Inbred BALB C, Osteosarcoma, biology, business.industry, Immunotherapy, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Female, Antibody, business, CD8, medicine.drug
الوصف: 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.
تدمد: 1537-4513
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d6ca3cc9745a2c31bc3766f9b378a4e
https://pubmed.ncbi.nlm.nih.gov/31219973
رقم الأكسشن: edsair.doi.dedup.....3d6ca3cc9745a2c31bc3766f9b378a4e
قاعدة البيانات: OpenAIRE