Decorin-armed oncolytic adenovirus promotes natural killers (NKs) activation and infiltration to enhance NK therapy in CRC model.


Journal

Molecular biomedicine
ISSN: 2662-8651
Titre abrégé: Mol Biomed
Pays: Singapore
ID NLM: 9918283581406676

Informations de publication

Date de publication:
01 Nov 2024
Historique:
received: 25 03 2024
accepted: 19 09 2024
medline: 1 11 2024
pubmed: 1 11 2024
entrez: 1 11 2024
Statut: epublish

Résumé

Colorectal cancer (CRC) is a prevalent malignant tumor of the gastrointestinal system, with the third and second highest incidence and mortality rates globally in 2020, respectively. Immunotherapy has developed rapidly in recent years. Natural killer (NK) cells have received increasing attention in the field of tumor immunotherapy due to their recognition and killing tumor cells without the limitations of major histocompatibility complexes. However, constraints within the tumor microenvironment that impede the infiltration and proliferation of NK cells result in poor efficacy of NK cell therapy for solid tumors. Oncolytic viral therapy is an immunogenic treatment with the potential to enhance anti-tumour immune responses and promote immune cell infiltration. In this study, we synergistically combine NK cells with an oncolytic adenovirus carrying Decorin (rAd.DCN) for the treatment of colorectal cancer (CRC) in a xenograft mouse model. By using Flow cytometry, real-time quantitative PCR and Calcein-AM release assay, we found that rAd.DCN could effectively promote proliferation, activation and degranulation of NK cells, up-regulate expression and secretion of NK cell killing activity-related factors, and enhance their killing activity. The efficacy is better than that of the blank control oncolytic virus rAd.Null. Combined treatment significantly inhibited tumor growth, increased the number of NK cells in peripheral blood, promoted the killing function of NK cells, and increased the expression levels of perforin and IFN-γ. At the same time, more NK cells were recruited to infiltrate tumor tissue. Our study established the feasibility of combination NK cells and oncolytic adenovirus application, thus expanding the scope of potentially curative treatments for NK cells in CRC.

Identifiants

pubmed: 39482550
doi: 10.1186/s43556-024-00212-z
pii: 10.1186/s43556-024-00212-z
doi:

Substances chimiques

Decorin 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

48

Informations de copyright

© 2024. The Author(s).

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Auteurs

Xue Li (X)

College of Life Science, Anhui Medical University, Hefei, 230032, P.R. China.
Beijing Institute of Radiation Medicine, Beijing, 100850, China.

Yuning Zhang (Y)

Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, 100071, China.

Zhuang Mao (Z)

Beijing Institute of Radiation Medicine, Beijing, 100850, China.

Huiqiang Zhao (H)

Department of Healthcare, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China.

Hu Cao (H)

Beijing Institute of Radiation Medicine, Beijing, 100850, China.

Jingyi Wang (J)

Beijing Jingda Biotechnology Co. Ltd, Beijing, 102629, China.

Wei Liu (W)

Beijing Jingda Biotechnology Co. Ltd, Beijing, 102629, China.

Shiyun Dai (S)

Beijing Jingda Biotechnology Co. Ltd, Beijing, 102629, China.

Yuefeng Yang (Y)

Department of Experimental Medical Science, Ningbo No.2 Hospital, Ningbo, 315010, China.

Yuanyuan Huang (Y)

Beijing Jingda Biotechnology Co. Ltd, Beijing, 102629, China. huangyy@jingdabio.com.

Hua Wang (H)

College of Life Science, Anhui Medical University, Hefei, 230032, P.R. China. 18511712135@163.com.
Beijing Institute of Radiation Medicine, Beijing, 100850, China. 18511712135@163.com.

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