دورية أكاديمية
Deciphering the potential role of PGRN in regulating CD8+ T cell antitumor immunity
| العنوان: | Deciphering the potential role of PGRN in regulating CD8+ T cell antitumor immunity |
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| المؤلفون: | Wenyu Zhang, Huan Qin, Guosheng Wang, Jing Zhang, Wenjuan He, Chunmei Feng, Huimin Wan, Feilong Wang, Zhongliang Guo |
| المصدر: | Cell Death Discovery, Vol 10, Iss 1, Pp 1-10 (2024) |
| بيانات النشر: | Nature Publishing Group, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens LCC:Cytology |
| مصطلحات موضوعية: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671 |
| الوصف: | Abstract A key factor contributing to resistance in immune checkpoint blockade (ICB) therapies is CD8+ T-cell tolerance in the tumor microenvironment (TME), partly resulting from upregulating coinhibitory receptors. Here, we describe the role of PGRN as a coinhibitory molecule that modulates the antitumor response of CD8+ T cells, thus presenting a novel immunosuppressive target for lung cancer. The in vivo subcutaneous transplanted lung cancer model showed that PGRN expression was elevated on CD8+ T cells that infiltrated transplanted lung cancers. Furthermore, PGRN deficiency was found to specifically encourage the infiltration of CD8+ T cells, enhance their proliferation, migration, and activation, and resist apoptosis, ultimately inhibiting tumor growth. This was achieved by PGRN knockout, increasing the production of T cell chemokine CCL3, which boosts the antitumor immune response induced by CD8+ T cells. Critically, the PD-L1 inhibitor exhibited a synergistic effect in enhancing the antitumor response in PGRN–/– mice. In summary, our findings highlight the significance of PGRN as a novel target for boosting CD8+ T cells antitumor immunity and its potential to overcome the resistance in ICB therapy. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2058-7716 |
| Relation: | https://doaj.org/toc/2058-7716 |
| DOI: | 10.1038/s41420-024-02001-7 |
| URL الوصول: | https://doaj.org/article/39e4e06eb0944e2b92a6f32ca6f19c11 |
| رقم الأكسشن: | edsdoj.39e4e06eb0944e2b92a6f32ca6f19c11 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20587716 |
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| DOI: | 10.1038/s41420-024-02001-7 |