Neutralizing IL-16 enhances the efficacy of targeting Aurora-A therapy in colorectal cancer with high lymphocyte infiltration through restoring anti-tumor immunity
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Le résumé fourni par la source
Abstract Cancer cells can evade immune elimination by activating immunosuppressive signaling pathways in the tumor microenvironment (TME). Targeting immunosuppressive signaling pathways to promote antitumor immunity has become an attractive strategy for cancer therapy. Aurora-A is a well-known oncoprotein that plays a critical role in tumor progression, and its inhibition is considered a promising strategy for treating cancers. However, targeting Aurora-A has not yet got a breakthrough in clinical trials. Recent reports have indicated that inhibition of oncoproteins may reduce antitumor immunity, but the role of tumor-intrinsic Aurora-A in regulating antitumor immunity remains unclear. In this study, we demonstrated that in tumors with high lymphocyte infiltration (hot tumors), higher tumor-intrinsic Aurora-A expression is associated with a better prognosis in CRC patients. Mechanically, tumor-intrinsic Aurora-A promotes the cytotoxic activity of CD8+ T cells in immune hot CRC via negatively regulating interleukin-16 (IL-16), and the upregulation of IL-16 may impair the therapeutic effect of Aurora-A inhibition. Consequently, combination treatment with IL-16 neutralization improves the therapeutic response to Aurora-A inhibitors in immune hot CRC tumors. Our study provides evidence that tumor-intrinsic Aurora-A contributes to anti-tumor immunity depending on the status of lymphocyte infiltration, highlighting the importance of considering this aspect in cancer therapy targeting Aurora-A. Importantly, our results suggest that combining Aurora-A inhibitors with IL-16-neutralizing antibodies may represent a novel and effective approach for cancer therapy, particularly in tumors with high levels of lymphocyte infiltration.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Neutralizing IL-16 enhances the efficacy of targeting Aurora-A therapy in colorectal cancer with high lymphocyte infiltration through restoring anti-tumor immunity
- Date Crossref
- 30/01/2024
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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National Cheng Kung University Department of Oncology pays non établi dans la noticeUniversité ou école supérieure
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Chi Mei Medical Center Department of Pathology pays non établi dans la noticeÉtablissement de santé
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National Health Research Institutes pays non établi dans la noticeOrganisation à but non lucratif
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National Cheng Kung University Hospital pays non établi dans la noticeÉtablissement de santé
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Kuo General Hospital Department of Pathology pays non établi dans la noticeÉtablissement de santé
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Kaohsiung Medical University pays non établi dans la noticeUniversité ou école supérieure
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College of Medicine The Institute of Basic Medical Sciences pays non établi dans la noticeUniversité ou école supérieure
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College of Bioscience and Biotechnology Department of Biotechnology and Bioindustry Sciences pays non établi dans la noticeUniversité ou école supérieure
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National Institute of Cancer Research pays non établi dans la noticeStructure de recherche
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University Center for Bioscience and Biotechnology pays non établi dans la noticeUniversité ou école supérieure
Department of Oncology — National Cheng Kung University, Department of Pathology — Chi Mei Medical Center et National Health Research Institutes, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.