دورية أكاديمية
Targeting IGF2-IGF1R Signaling to Reprogram the Tumor Microenvironment for Enhanced Viro-Immunotherapy.
| العنوان: | Targeting IGF2-IGF1R Signaling to Reprogram the Tumor Microenvironment for Enhanced Viro-Immunotherapy. |
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| المؤلفون: | Noh MH; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA., Kang JM; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.; Department of Pediatric Hematology & Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA., Miller AA; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Science, Houston, TX 77025, USA., Nguyen G; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA., Huang M; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA., Shim JS; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA., Bueso-Perez AJ; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA., Murphy SA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Science, Houston, TX 77025, USA.; Georgia Cancer Center and Department of Pathology, Medical College of Georgia, Augusta University, 1410 Laney Walker Blvd, CN-3311, Augusta, GA 30912, USA., Rivera-Caraballo KA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Science, Houston, TX 77025, USA.; Georgia Cancer Center and Department of Pathology, Medical College of Georgia, Augusta University, 1410 Laney Walker Blvd, CN-3311, Augusta, GA 30912, USA., Otani Y; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.; Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan., Kim E; Department of Biochemistry, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.; Department of Food and Nutriton, Kongju National University, Yesan, Chungnam, 32439, South Korea., Yoo SH; Department of Biochemistry, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA., Yan Y; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA., Banasavadi-Siddegowda Y; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20852, USA., Nakashima H; Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA., Chiocca EA; Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA., Kaur B; Georgia Cancer Center and Department of Pathology, Medical College of Georgia, Augusta University, 1410 Laney Walker Blvd, CN-3311, Augusta, GA 30912, USA., Zhao Z; Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Lee TJ; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Science, Houston, TX 77025, USA., Yoo JY; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Science, Houston, TX 77025, USA. |
| المصدر: | Neuro-oncology [Neuro Oncol] 2024 Jun 10. Date of Electronic Publication: 2024 Jun 10. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 100887420 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-5866 (Electronic) Linking ISSN: 15228517 NLM ISO Abbreviation: Neuro Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2010- : Oxford : Oxford University Press Original Publication: 1999-<2002> : Charlottesville, VA : Carden Jennings Pub., |
| مستخلص: | Background: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME). Methods: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance. Results: Transcriptome analysis identified IGF2 as one of the top secreted proteins following oHSV treatment. Moreover, IGF2 expression was significantly upregulated in 10 out of 14 recurrent GBM patients after treatment with oHSV, rQNestin34.5v.2 (71.4%) (p=0.0020) (ClinicalTrials.gov, NCT03152318). Depletion of IGF2 substantially enhanced oHSV-mediated tumor cell killing in vitro and improved survival of mice bearing BCBM tumors in vivo. To mitigate the oHSV-induced IGF2 in the TME, we constructed a novel oHSV, oHSV-D11mt, secreting a modified IGF2R domain 11 (IGF2RD11mt) that acts as IGF2 decoy receptor. Selective blocking of IGF2 by IGF2RD11mt significantly increased cytotoxicity, reduced oHSV-induced neutrophils/PMN-MDSCs infiltration, and reduced secretion of immune suppressive/proangiogenic cytokines, while increased CD8+cytotoxic T lymphocytes (CTLs) infiltration, leading to enhanced survival in GBM or BCBM tumor-bearing mice. Conclusion: This is the first study reporting that oHSV-induced secreted IGF2 exerts a critical role in resistance to oHSV therapy, which can be overcome by oHSV-D11mt as a promising therapeutic advance for enhanced viro-immunotherapy. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.) |
| معلومات مُعتمدة: | R01 CA276942 United States CA NCI NIH HHS; R21 NS123685 United States NS NINDS NIH HHS |
| فهرسة مساهمة: | Keywords: Glioblastoma (GBM); Insulin-like growth factor 2 (IGF2); Insulin-like growth factor-1 receptor (IGF1R); Oncolytic herpes simplex virus-1 (oHSV); Tumor microenvironment (TME) |
| سلسلة جزيئية: | ClinicalTrials.gov NCT03152318 |
| تواريخ الأحداث: | Date Created: 20240610 Latest Revision: 20240711 |
| رمز التحديث: | 20240711 |
| DOI: | 10.1093/neuonc/noae105 |
| PMID: | 38853689 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1523-5866 |
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| DOI: | 10.1093/neuonc/noae105 |