Academic Journal
EP2 and EP4 blockade prevents tumor-induced suppressive features in human monocytic myeloid-derived suppressor cells
| العنوان: | EP2 and EP4 blockade prevents tumor-induced suppressive features in human monocytic myeloid-derived suppressor cells |
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| المؤلفون: | Cuenca-Escalona, Jorge, Subtil, Beatriz, Garcia-Perez, Alba, Cambi, Alessandra, de Vries, I. Jolanda M., Flórez-Grau, Georgina |
| المصدر: | Frontiers in Immunology ; volume 15 ; ISSN 1664-3224 |
| بيانات النشر: | Frontiers Media SA |
| سنة النشر: | 2024 |
| المجموعة: | Frontiers (Publisher - via CrossRef) |
| الوصف: | Tumors educate their environment to prime the occurrence of suppressive cell subsets, which enable tumor evasion and favors tumor progression. Among these, there are the myeloid-derived suppressor cells (MDSCs), their presence being associated with the poor clinical outcome of cancer patients. Tumor-derived prostaglandin E2 (PGE2) is known to mediate MDSC differentiation and the acquisition of pro-tumor features. In myeloid cells, PGE2 signaling is mediated via E-prostanoid receptor type 2 (EP2) and EP4. Although the suppressive role of PGE2 is well established in MDSCs, the role of EP2/4 on human MDSCs or whether EP2/4 modulation can prevent MDSCs suppressive features upon exposure to tumor-derived PGE2 is poorly defined. In this study, using an in vitro model of human monocytic-MDSCs (M-MDSCs) we demonstrate that EP2 and EP4 signaling contribute to the induction of a pro-tumor phenotype and function on M-MDSCs. PGE2 signaling via EP2 and EP4 boosted M-MDSC ability to suppress T and NK cell responses. Combined EP2/4 blockade on M-MDSCs during PGE2 exposure prevented the occurrence of these suppressive features. Additionally, EP2/4 blockade attenuated the suppressive phenotype of M-MDSCs in a 3D coculture with colorectal cancer patient-derived organoids. Together, these results identify the role of tumor-derived PGE2 signaling via EP2 and EP4 in this human M-MDSC model, supporting the therapeutic value of targeting PGE2-EP2/4 axis in M-MDSCs to alleviate immunosuppression and facilitate the development of anti-tumor immunity. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| DOI: | 10.3389/fimmu.2024.1355769 |
| DOI: | 10.3389/fimmu.2024.1355769/full |
| الاتاحة: | http://dx.doi.org/10.3389/fimmu.2024.1355769 https://www.frontiersin.org/articles/10.3389/fimmu.2024.1355769/full |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.49DA006 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2024.1355769 |
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