دورية أكاديمية
ALCAM-mediated cDC1 CD8 T cells interactions are suppressed in advanced lung tumors
| العنوان: | ALCAM-mediated cDC1 CD8 T cells interactions are suppressed in advanced lung tumors |
|---|---|
| المؤلفون: | Luciano G. Morosi, Giulia M. Piperno, Lucía López, Roberto Amadio, Sonal Joshi, Alessandra Rustighi, Giannino Del Sal, Federica Benvenuti |
| المصدر: | OncoImmunology, Vol 13, Iss 1 (2024) |
| بيانات النشر: | Taylor & Francis Group, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | ALCAM, cDC1, immunological synapse, lung cancer, NSCLC, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Conventional type 1 dendritic cells (cDC1) are critical regulators of anti-tumoral T-cell responses. The structure and abundance of intercellular contacts between cDC1 and CD8 T cells in cancer tissues is important to determine the outcome of the T-cell response. However, the molecular determinants controlling the stability of cDC1–CD8 interactions during cancer progression remain poorly investigated. Here, we generated a genetic model of non-small cell lung cancer crossed to a fluorescent cDC1 reporter (KP-XCR1venus) to allow the detection of cDC1-CD8T cell clusters in tumor tissues across tumor stages. We found that cDC1-CD8 clusters are abundant and productive at the early stages of tumor development but progressively diminish in advanced tumors. Transcriptional profiling and flow cytometry identified the adhesion molecule ALCAM/CD166 (Activated Leukocyte Cell Adhesion Molecule, ligand of CD6) as highly expressed by lung cDC1 and significantly downregulated in advanced tumors. Analysis of human datasets indicated that ALCAM is downregulated in non-small cell lung cancer and its expression correlates to better prognosis. Mechanistically, triggering ALCAM on lung cDC1 induces cytoskeletal remodeling and contact formation whereas its blockade prevents T-cell activation. Together, our results indicate that ALCAM is important to stabilize cDC1–CD8 interactions at early tumor stages, while its loss in advanced tumors contributes to immune evasion. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2162402X 2162-402X |
| Relation: | https://doaj.org/toc/2162-402X |
| DOI: | 10.1080/2162402X.2024.2367843 |
| URL الوصول: | https://doaj.org/article/c26f54c4f1384cff8d47264b180e0d57 |
| رقم الأكسشن: | edsdoj.26f54c4f1384cff8d47264b180e0d57 |
| قاعدة البيانات: | Directory of Open Access Journals |
PDF full text from Publisher 
Full Text Finder | تدمد: | 2162402X |
|---|---|
| DOI: | 10.1080/2162402X.2024.2367843 |