| Autor: |
Jian Huang, Liming Huang, Xuan Shao, Lu Cheng, Zhou Jiang, Qiannan Ding, Shimin Wang, Jun Pan, Pu Cheng, Guoming Hu |
| Rok vydání: |
2023 |
| DOI: |
10.1158/2326-6066.c.6549817.v1 |
| Popis: |
The tumor microenvironment induces immunosuppression via recruiting and expanding suppressive immune cells such as regulatory T cells (Treg) to promote cancer progression. In this study, we documented that tumor-infiltrating CD73+ γδTregs were the predominant Tregs in human breast cancer and exerted more potent immunosuppressive activity than CD4+ or CD8+ Tregs. We further demonstrated that cancer-associated fibroblast (CAF)–derived IL6, rather than TGFβ1, induced CD73+ γδTreg differentiation from paired normal breast tissues via the IL6/STAT3 pathway to produce more adenosine and become potent immunosuppressive T cells. CD73+ γδTregs could in turn promote IL6 secretion by CAFs through adenosine/A2BR/p38MAPK signaling, thereby forming an IL6–adenosine positive feedback loop. CD73+ γδTreg infiltration also impaired the tumoricidal functions of CD8+ T cells and significantly correlated with worse prognosis of patients. The data indicate that the IL6–adenosine loop between CD73+ γδTregs and CAFs is important to promote immunosuppression and tumor progression in human breast cancer, which may be critical for tumor immunotherapy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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