Tumor-Induced Tolerance and Immune Suppression Depend on the C/EBPβ Transcription Factor

被引：752

作者：

Marigo, Ilaria ^{[2
]}

Bosio, Erika ^{[3
]}

Solito, Samantha ^{[2
]}

Mesa, Circe ^{[4
]}

Fernandez, Audry ^{[4
]}

Dolcetti, Luigi ^{[5
]}

Ugel, Stefano ^{[2
,5
]}

Sonda, Nada ^{[5
]}

Bicciato, Silvio ^{[6
]}

Falisi, Erika ^{[2
]}

Calabrese, Fiorella ^{[3
]}

Basso, Giuseppe ^{[7
]}

Zanovello, Paola ^{[1
,2
]}

Cozzi, Emanuele ^{[8
]}

Mandruzzato, Susanna ^{[1
,2
]}

Bronte, Vincenzo ^{[1
]}

机构：

[1] IRCCS, IOV, I-35128 Padua, Italy

[2] Univ Padua, Dept Oncol & Surg Sci, I-35128 Padua, Italy

[3] Univ Padua, Dept Med Diagnost Sci & Special Therapies, I-35128 Padua, Italy

[4] Ctr Mol Immunol, Havana 16040, Cuba

[5] Venetian Inst Mol Med, I-35129 Padua, Italy

[6] Univ Modena & Reggio Emilia, Dept Biomed Sci, Ctr Genome Res, I-41100 Modena, Italy

[7] Univ Padua, Dept Pediat, I-35100 Padua, Italy

[8] Padua Hosp, Direz Sanit, I-35128 Padua, Italy

来源：

IMMUNITY | 2010年 / 32卷 / 06期

关键词：

COLONY-STIMULATING FACTOR; T-CELL RESPONSES; DIFFERENTIATION; ISOFORMS; CANCER; INHIBITION; INDUCTION; SUBSETS; ANTIGEN;

D O I：

10.1016/j.immuni.2010.05.010

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Tumor growth is associated with a profound alteration in myelopoiesis, leading to recruitment of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs). We showed that among factors produced by various experimental tumors, the cytokines GM-CSF, G-CSF, and IL-6 allowed a rapid generation of MDSCs from precursors present in mouse and human bone marrow (BM). BM-MDSCs induced by GM-CSF+IL-6 possessed the highest tolerogenic activity, as revealed by the ability to impair the priming of CD8(+) T cells and allow long term acceptance of pancreatic islet allografts. Cytokines inducing MDSCs acted on a common molecular pathway and the immunoregulatory activity of both tumor-induced and BM-derived MDSCs was entirely dependent on the C/EBP beta transcription factor. Adoptive transfer of tumor antigen-specific CD8(+) T lymphocytes resulted in therapy of established tumors only in mice lacking C/EBP beta in the myeloid compartment, suggesting that C/EBP beta is a critical regulator of the immunosuppressive environment created by growing cancers.

引用

页码：790 / 802

页数：13

共 35 条

[1] Identification of a CD11b+/Gr-1+/CD31+ myeloid progenitor capable of activating or suppressing CD8+ T cells [J].