Academic Journal

Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma

التفاصيل البيبلوغرافية
العنوان: Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma
المؤلفون: Yuchen Zhang, Junnian Zheng, Li Sun, Guangya Zhao, Yingxiang Shao, Bowen Lu, Jiage Ding, Yanyan Zheng, Renjin Chen, Dafei Chai, Jiawei Wang, Zichun Zhang, Xiaohui Xie
المصدر: Journal for ImmunoTherapy of Cancer, Vol 13, Iss 1 (2025)
بيانات النشر: BMJ Publishing Group, 2025.
سنة النشر: 2025
المجموعة: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Background Siglec-E is an immune checkpoint inhibitory molecule. Expression of Siglec-E on the immune cells has been shown to promote tumor regression. This study aimed to develop an adenovirus (Ad) vaccine targeting Siglec-E and carbonic anhydrase IX (CAIX) (Ad-Siglec-E/CAIX) and to evaluate its potential antitumor effects in several preclinical renal cancer models.Methods Ad vaccines encoding Siglec-E or CAIX were developed and evaluated for their therapeutic potential in mouse subcutaneous, lung metastatic, and orthotopic tumor models. The expression of Ad-Siglec-E/CAIX was confirmed via PCR and flow cytometry. Immune responses induced by Ad-Siglec-E/CAIX were assessed in vitro and in vivo using flow cytometry, immunohistochemistry, ELISA, histological analysis, cell proliferation, enzyme-linked immunosorbent spot, cytotoxic T lymphocytes (CTL) killing, and cell depletion assays.Results Ad-Siglec-E/CAIX vaccine induced the increase of tumor-infiltrated immune cells, and significantly suppressed the subcutaneous tumor growth of renal carcinoma. Immunization with Ad-Siglec-E/CAIX promoted the induction and maturation of CD11c+ dendritic cells and their subsets, which in turn enhanced tumor-specific CD8+ T cell immune responses, as evidenced by increased CD8+ T cell proliferation and CTL activity. Importantly, the deletion of CD8+ T cells in vivo abolished the antitumor effect of the Ad-Siglec-E/CAIX vaccine, highlighting the essential role of functional CD8+ T cell responses. The potent therapeutic efficacy of the Ad-Siglec-E/CAIX vaccine was also observed in lung metastasis and orthotopic tumor models through tumor-specific CD8+ T cell immune responses.Conclusions Our results indicate that targeting Siglec-E enhances the therapeutic efficacy of Ad-CAIX against renal carcinoma, providing a promising therapeutic option for solid tumors.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2051-1426
Relation: https://jitc.bmj.com/content/13/1/e010521.full; https://doaj.org/toc/2051-1426
DOI: 10.1136/jitc-2024-010521
URL الوصول: https://doaj.org/article/a6285c4a813d45ce9201fd2d54d2b488
رقم الانضمام: edsdoj.6285c4a813d45ce9201fd2d54d2b488
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20511426
DOI:10.1136/jitc-2024-010521