ID | 65168 |
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Nakasuka, Takamasa
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ohashi, Kadoaki
Department of Respiratory Medicine, Okayama University Hospital
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Nishii, Kazuya
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hirabae, Atsuko
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Okawa, Sachi
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Tomonobu, Nahoko
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Takada, Kenji
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ando, Chihiro
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Watanabe, Hiromi
Department of Respiratory Medicine, Okayama University Hospital
Makimoto, Go
Department of Respiratory Medicine, Okayama University Hospital
Ninomiya, Kiichiro
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine
Kaken ID
Fujii, Masanori
Department of Respiratory Medicine, Okayama University Hospital
Hotta, Katsuyuki
Center for Innovative Clinical Medicine, Okayama University Hospital
Kumon, Hiromi
Innovation Center Okayama for Nanobio-targeted Therapy, Okayama University
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Maeda, Yoshinobu
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Kiura, Katsuyuki
Department of Respiratory Medicine, Okayama University Hospital
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Abstract | Objectives: No immunotherapeutic protocol has yet been established in never-smoking patients with lung cancer harboring driver oncogenic mutations, such as epidermal growth factor receptor (EGFR) mutations. The immunostimulatory effect of Ad-REIC, a genetically engineered adenovirus vector expressing a tumor suppressor gene, reduced expression in immortalized cells (REIC), has been investigated in clinical trials for various solid tumors. However, the immunostimulatory effect of the Ad-REIC in EGFR-mutant lung cancer with a non-inflamed tumor microenvironment (TME) has not been explored.
Materials and methods: We used a syngeneic mouse model developed by transplanting Egfr-mutant lung cancer cells into single or double flanks of C57BL/6J mice. Ad-SGE-REIC, a 2nd-generation vector with an enhancer sequence, was injected only into the tumors from one flank, and its antitumor effects were assessed. Tumor-infiltrating cells were evaluated using immunohistochemistry or flow cytometry. The synergistic effects of Ad-SGE-REIC and PD-1 blockade were also examined. Results: Injection of Ad-SGE-REIC into one side of the tumor induced not only a local antitumor effect but also a bystander abscopal effect in the non-injected tumor, located on the other flank. The number of PD-1+CD8+ T cells increased in both injected and non-injected tumors. PD-1 blockade augmented the local and abscopal antitumor effects of Ad-SGE-REIC by increasing the number of CD8+ T cells in the TME of Egfr-mutant tumors. Depletion of CD8+ cells reverted the antitumor effect, suggesting they contribute to antitumor immunity. Conclusion: Ad-SGE-REIC induced systemic antitumor immunity by modifying the TME status from non-inflamed to inflamed, with infiltration of CD8+ T cells. Additionally, in Egfr-mutant lung cancer, this effect was enhanced by PD-1 blockade. These findings pave the way to establish a novel combined immunotherapy strategy with Ad-SGE-REIC and anti-PD-1 antibody for lung cancer with a non-inflamed TME. |
Keywords | EGFR mutation
Non-small cell lung cancer
Antitumor immunity
Non-inflamed tumor
Ad-SGE-REIC
Gene therapy
PD-1
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Note | ©2023 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 License. http://creativecommons.org/licenses/by-nc-nd/4.0/. This is the accepted manuscript version. The formal published version is available at https://doi.org/10.1016/j.lungcan.2023.01.018.
This fulltext file will be available in Apr. 2024.
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Published Date | 2023-04
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Publication Title |
Lung Cancer
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Volume | volume178
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Publisher | Elsevier BV
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Start Page | 1
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End Page | 10
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ISSN | 0169-5002
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NCID | AA10785743
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © 2023 Elsevier B.V.
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File Version | author
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Related Url | isVersionOf https://doi.org/10.1016/j.lungcan.2023.01.018
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License | http://creativecommons.org/licenses/by-nc-nd/4.0/
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Funder Name |
Japan Society for the Promotion of Science
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助成番号 | 22H03078
19H03667
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