Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells.
Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells.
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DOI：
10.1158/0008-5472.can-07-6621
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发表时间：
2008-07-01
期刊：
影响因子：
11.2
通讯作者：
Borrello I
中科院分区：
文献类型：
--
作者：
Serafini P;Mgebroff S;Noonan K;Borrello I
Tumor-induced T cell tolerance is a major mechanism that facilitates tumor progression and limits the efficacy of immune therapeutic interventions. Regulatory T cells (Treg) play a central role in the induction of tolerance to tumor antigens yet the precise mechanisms regulating its induction in vivo remain to be elucidated. Using the A20 B cell lymphoma model, here we identify myeloid derived suppressor cells (MDSCs) as the tolerogenic APCs capable of antigen uptake and presentation to tumor-specific Tregs. MDSC-mediated Treg induction requires arginase but is TGFβ independent. In vitro and in vivo inhibition of MDSC function respectively with NOHA or sildenafil abrogates Treg proliferation and tumor-induced tolerance in antigen specific T cells. These findings establish a role for MDSCs in antigen-specific tolerance induction through preferential antigen uptake mediating the recruitment and expansion of Tregs. Furthermore, therapeutic interventions such as in vivo phosphodiesterase 5 (PDE-5)-inhibition which effectively abrogate the immunosuppressive role of MDSCs and reduce Treg numbers, may play a critical role in delaying and/or reversing tolerance induction.
