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Published in: Cancer Immunology, Immunotherapy 6/2022

Open Access 21-10-2021 | Lung Cancer | Original Article

Immunogenic senescence sensitizes lung cancer to LUNX-targeting therapy

Authors: Defeng Jiao, Xiaohu Zheng, Xianghui Du, Dong Wang, Ziming Hu, Rui Sun, Zhigang Tian, Binqing Fu, Haiming Wei

Published in: Cancer Immunology, Immunotherapy | Issue 6/2022

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Abstract

The higher immunogenicity of tumors usually predicts favorable therapeutic responses. Tumor antigens dominate the immunogenic character within tumors. We investigated if there was a targetable tumor antigen during immunogenic chemotherapy within lung cancer. Chemotherapy-induced immunogenic senescence was demonstrated using a multi-marker, three-step workflow, and RNA-sequencing data. The ability of anti-lung-specific X protein (LUNX) antibody to suppress the survival of senescent lung cancer cells was evaluated in vitro and in vivo using real-time cytotoxicity analysis and xenograft mouse models, respectively. The induction of cellular senescence by immunogenic chemotherapy boosted cell-surface shuttling of LUNX and enhanced the immunogenic features of senescent tumor cells, which sensitized lung cancer cells to anti-LUNX antibody-mediated therapy and contributed to tumor suppression. The immunogenic senescence-mediated anti-tumor response was triggered by the direct action of antibody on tumor cells, strengthened by natural-killer cells through an antibody-dependent cell-mediated cytotoxicity response, and ultimately, led to tumor control. Our findings suggest that LUNX is a lung cancer targetable-immunogenic antigen. The proportion of lung cancers responding to LUNX-targeting therapy could be expanded substantially by immunogenic chemotherapy that induces senescence-associated translocation of LUNX to the plasma membrane.
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Metadata
Title
Immunogenic senescence sensitizes lung cancer to LUNX-targeting therapy
Authors
Defeng Jiao
Xiaohu Zheng
Xianghui Du
Dong Wang
Ziming Hu
Rui Sun
Zhigang Tian
Binqing Fu
Haiming Wei
Publication date
21-10-2021
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 6/2022
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-021-03077-1

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