Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function.
Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function.
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DOI：
10.1084/jem.20061104
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发表时间：
2006-11-27
期刊：
影响因子：
--
通讯作者：
Borrello I
中科院分区：
文献类型：
--
作者：
Serafini P;Meckel K;Kelso M;Noonan K;Califano J;Koch W;Dolcetti L;Bronte V;Borrello I
Phosphodiesterase-5 (PDE5) inhibitors (sildenafil, tadalafil, and vardenafil) are agents currently in clinical use for nonmalignant conditions. We report the use of PDE5 inhibitors as modulators of the antitumor immune response. In several mouse tumor models, PDE5 inhibition reverses tumor-induced immunosuppressive mechanisms and enables a measurable antitumor immune response to be generated that substantially delays tumor progression. In particular, sildenafil, down-regulates arginase 1 and nitric oxide synthase–2 expression, thereby reducing the suppressive machinery of CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSCs) recruited by growing tumors. By removing these tumor escape mechanisms, sildenafil enhances intratumoral T cell infiltration and activation, reduces tumor outgrowth, and improves the antitumor efficacy of adoptive T cell therapy. Sildenafil also restores in vitro T cell proliferation of peripheral blood mononuclear cells from multiple myeloma and head and neck cancer patients. In light of the recent data that enzymes mediating MDSC-dependent immunosuppression in mice are active also in humans, these findings demonstrate a potentially novel use of PDE5 inhibitors as adjuncts to tumor-specific immune therapy.
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影响因子：
15.3
作者：
Pekarek, Lisa A.;Starr, Barbara A.;Toledano, Alicia Y.;Schreiber, Hans
通讯作者：
Schreiber, Hans
影响因子：
4.4
作者：
Bronte, V;Serafini, P;Zanovello, P
通讯作者：
Zanovello, P
影响因子：
4
作者：
NANNI, P;DEGIOVANNI, C;PRODI, G
通讯作者：
PRODI, G
DOI：
10.1073/pnas.93.18.9730
发表时间：
1996-09-03
影响因子：
11.1
作者：
Huang, AYC;Gulden, PH;Jaffee, EM
通讯作者：
Jaffee, EM
DOI：
10.1073/pnas.90.8.3539
发表时间：
1993-04-15
影响因子：
11.1
作者：
DRANOFF, G;JAFFEE, E;MULLIGAN, RC
通讯作者：
MULLIGAN, RC