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Cited by 45Autophagy in Disease and TherapyCancer Immunotherapy and BiomarkersCell death mechanisms and regulation

Targeting autophagy enhances atezolizumab-induced mitochondria-related apoptosis in osteosarcoma

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Liu, Zhuochao, Wang, Hongyi, Hu, Chuanzhen, Wu, Chuanlong, Wang, Jun, Hu, Fangqiong, Fu, Yucheng, Wen, Junxiang +1 more·2021·Cell Death & Disease
DOI 10.1038/s41419-021-03449-6PMC PMC7870858
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Abstract

In this study, we identified the multifaceted effects of atezolizumab, a specific monoclonal antibody against PD-L1, in tumor suppression except for restoring antitumor immunity, and investigated the promising ways to improve its efficacy. Atezolizumab could inhibit the proliferation and induce immune-independent apoptosis of osteosarcoma cells. With further exploration, we found that atezolizumab could impair mitochondria of osteosarcoma cells, resulting in increased release of reactive oxygen species and cytochrome-c, eventually leading to mitochondrial-related apoptosis via activating JNK pathway. Nevertheless, the excessive release of reactive oxygen species also activated the protective autophagy of osteosarcoma cells. Therefore, when we combined atezolizumab with autophagy inhibitors, the cytotoxic effect of atezolizumab on osteosarcoma cells was significantly enhanced in vitro. Further in vivo experiments also confirmed that atezolizumab combined with chloroquine achieved the most significant antitumor effect. Taken together, our study indicates that atezolizumab can induce mitochondrial-related apoptosis and protective autophagy independently of the immune system, and targeting autophagy is a promising combinatorial approach to amplify its cytotoxicity.

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  • Blocking the protective autophagy induced by atezolizumab could significantly amplify its anti-tumor effect on osteosarcoma cells.

    “They performed further studies in vitro and in vivo and demonstrated that blocking the protective autophagy induced by atezolizumab could significantly amplify its anti-tumor effect on osteosarcoma cells [88].”

    From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [88]

  • Atezolizumab inhibits proliferation and induces immune-independent apoptosis of osteosarcoma cells through increasing the release of ROS and cytochrome-c.

    “Liu et al. reported that atezolizumab (anti PD-L1 antibody) inhibits proliferation and induces immune-independent apoptosis of osteosarcoma cells through increasing the release of ROS and cytochrome-c.”

    From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [88]

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Cited by

Sorted by citations

Authors
Liu, Z., Wang, H., Hu, C., Wu, C., Wang, J., Hu, F., Fu, Y., Wen, J., & Zhang, W.
Affiliations
  • Shanghai Jiao Tong University (CN)
  • Tongji University (CN)
Corresponding author
  • Wen, Junxiang
  • Zhang, Weibin
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2021-02-08
Volume
12
Issue
2
Pages
164-164
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/s41419-021-03449-6
PMC
PMC7870858
OpenAlex
W3127611956
Cited by
45
References
4
Citations by year
2026: 8 · 2025: 6 · 2024: 10 · 2023: 7 · 2022: 11 · 2021: 3
FWCI
5.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81802169, 81702661, 82072957, 81802840)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
atezolizumab, osteosarcoma, autophagy, mitochondrial apoptosis, PD-L1 blockade, JNK signaling, reactive oxygen species, cytochrome c release, chloroquine, autophagy inhibitors, combination therapy
MeSH terms
Immune Checkpoint Inhibitors, Animals, Antineoplastic Combined Chemotherapy Protocols, Autophagy, Bone Neoplasms, Chloroquine, Humans, Male, Mitochondria, Osteosarcoma, Signal Transduction, Mice, SCID, Apoptosis, Reactive Oxygen Species, Xenograft Model Antitumor Assays, Cytochromes c, Cell Line, Tumor, JNK Mitogen-Activated Protein Kinases, Cell Proliferation, Mice, Tumor Microenvironment, B7-H1 Antigen, Antibodies, Monoclonal, Humanized

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