Academic Journal
UM171A-induced ROS promote antigen cross-presentation of immunogenic peptides by bone marrow-derived mesenchymal stromal cells
| العنوان: | UM171A-induced ROS promote antigen cross-presentation of immunogenic peptides by bone marrow-derived mesenchymal stromal cells |
|---|---|
| المؤلفون: | Salame, Natasha, Bikorimana, Jean-Pierre, El-Hachem, Nehme, Saad, Wael, Kurdi, Mazen, Zhao, Jing, Eliopoulos, Nicoletta, Shammaa, Riam, Rafei, Moutih |
| المساهمون: | Cancer Research Society |
| المصدر: | Stem Cell Research & Therapy ; volume 13, issue 1 ; ISSN 1757-6512 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| الوصف: | Background Mesenchymal stromal cells (MSCs) have been extensively used in the clinic due to their exquisite tissue repair capacity. However, they also hold promise in the field of cellular vaccination as they can behave as conditional antigen presenting cells in response to interferon (IFN)-gamma treatment under a specific treatment regimen. This suggests that the immune function of MSCs can be pharmacologically modulated. Given the capacity of the agonist pyrimido-indole derivative UM171a to trigger the expression of various antigen presentation-related genes in human hematopoietic progenitor cells, we explored the potential use of UM171a as a means to pharmacologically instill and/or promote antigen presentation by MSCs. Methods Besides completing a series of flow-cytometry-based phenotypic analyses, several functional antigen presentation assays were conducted using the SIINFEKL-specific T-cell clone B3Z. Anti-oxidants and electron transport chain inhibitors were also used to decipher UM171a’s mode of action in MSCs. Finally, the potency of UM171a-treated MSCs was evaluated in the context of therapeutic vaccination using immunocompetent C57BL/6 mice with pre-established syngeneic EG.7T-cell lymphoma. Results Treatment of MSCs with UM171a triggered potent increase in H2-K b cell surface levels along with the acquisition of antigen cross-presentation abilities. Mechanistically, such effects occurred in response to UM171a-mediated production of mitochondrial-derived reactive oxygen species as their neutralization using anti-oxidants or Antimycin-A mitigated MSCs’ ability to cross-present antigens. Processing and presentation of the immunogenic ovalbumin-derived SIINFEKL peptide was caused by de novo expression of the Psmb8 gene in response to UM171a-triggered oxidative stress. When evaluated for their anti-tumoral properties in the context of therapeutic vaccination, UM171a-treated MSC administration to immunocompetent mice with pre-established T-cell lymphoma controlled tumor growth resulting in 40% ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1186/s13287-021-02693-z |
| DOI: | 10.1186/s13287-021-02693-z.pdf |
| DOI: | 10.1186/s13287-021-02693-z/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1186/s13287-021-02693-z https://link.springer.com/content/pdf/10.1186/s13287-021-02693-z.pdf https://link.springer.com/article/10.1186/s13287-021-02693-z/fulltext.html |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.41E6AB0E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s13287-021-02693-z |
|---|