Combination Treatment with Sublethal Ionizing Radiation and the Proteasome Inhibitor Bortezomib Enhances Death Receptor Mediated Apoptosis and Anti Tumor Immune Attack
Yazarlar (5)
Prof. Dr. Ercan ÇAÇAN
Tokat Gaziosmanpaşa Üniversitesi, Türkiye
Georgia State University, Amerika Birleşik Devletleri
Georgia State University, Amerika Birleşik Devletleri
American Cancer Society, Amerika Birleşik Devletleri
Georgia State University, Amerika Birleşik Devletleri
| Makale Türü |
Özgün Makale
|
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale |
| Dergi Adı | International Journal of Molecular Sciences |
| Dergi ISSN | 1661-6596 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q4 |
| Makale Dili | İngilizce |
| Basım Tarihi | 12-2015 |
| Cilt No | 16 |
| Sayı | 12 |
| Sayfalar | 30405 / 30421 |
| DOI Numarası | 10.3390/ijms161226238 |
| Makale Linki | http://www.mdpi.com/1422-0067/16/12/26238 |
| Özet |
| Sub-lethal doses of radiation can modulate gene expression, making tumor cells more susceptible to T-cell-mediated immune attack. Proteasome inhibitors demonstrate broad anti-tumor activity in clinical and pre-clinical cancer models. Here, we use a combination treatment of proteasome inhibition and irradiation to further induce immunomodulation of tumor cells that could enhance tumor-specific immune responses. We investigate the effects of the 26S proteasome inhibitor, bortezomib, alone or in combination with radiotherapy, on the expression of immunogenic genes in normal colon and colorectal cancer cell lines. We examined cells for changes in the expression of several death receptors (DR4, DR5 and Fas) commonly used by T cells for killing of target cells. Our results indicate that the combination treatment resulted in increased cell surface expression of death receptors by increasing their transcript levels. The combination treatment further increases the sensitivity of carcinoma cells to apoptosis through FAS and TRAIL receptors but does not change the sensitivity of normal non-malignant epithelial cells. Furthermore, the combination treatment significantly enhances tumor cell killing by tumor specific CD8+ T cells. This study suggests that combining radiotherapy and proteasome inhibition may simultaneously enhance tumor immunogenicity and the induction of antitumor immunity by enhancing tumor-specific T-cell activity. |
| Anahtar Kelimeler |
| Anti-tumor immunity | Death receptors | Proteasome | Radiation |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| WoS | 18 |
| SCOPUS | 22 |
| Google Scholar | 26 |