IL-10 Elicits IFNγ-Dependent Tumor Immune Surveillance

被引：365

作者：

Mumm, John B. ^{[1
]}

Emmerich, Jan ^{[1
]}

Zhang, Xueqing ^{[1
]}

Chan, Ivan ^{[1
]}

Wu, Lingling ^{[1
]}

Mauze, Smita ^{[1
]}

Blaisdell, Steven ^{[2
]}

Basham, Beth ^{[1
]}

Dai, Jie ^{[1
]}

Grein, Jeff ^{[1
]}

Sheppard, Catherine ^{[1
]}

Hong, Kyu ^{[1
]}

Cutler, Collette ^{[2
]}

Turner, Scott ^{[1
]}

LaFace, Drake ^{[1
]}

Kleinschek, Melanie ^{[1
]}

Judo, Michael ^{[1
]}

Ayanoglu, Gulesi ^{[1
]}

Langowski, John ^{[1
]}

Gu, Danling ^{[1
]}

Paporello, Brittany ^{[2
]}

Murphy, Erin ^{[1
]}

Sriram, Venkataraman ^{[1
]}

Naravula, Saraswathi ^{[1
]}

Desai, Bela ^{[1
]}

Medicherla, Satya ^{[1
]}

Seghezzi, Wolfgang ^{[1
]}

McClanahan, Terrill ^{[1
]}

Cannon-Carlson, Susan ^{[2
]}

Beebe, Amy M. ^{[1
]}

Oft, Martin ^{[1
]}

机构：

[1] Merck Res Labs, Palo Alto, CA 94301 USA

[2] Merck Res Labs, Biotechnol Dev, Union, NJ 07083 USA

来源：

CANCER CELL | 2011年 / 20卷 / 06期

关键词：

EFFECTOR T-CELLS; INTERLEUKIN-10; CANCER; MELANOMA; INDUCTION; PROMOTES; BREAST; HOST;

D O I：

10.1016/j.ccr.2011.11.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tumor immune surveillance and cancer immunotherapies are thought to depend on the intratumoral infiltration of activated CD8(+) T cells. Intratumoral CD8(+) T cells are rare and lack activity. IL-10 is thought to contribute to the underlying immune suppressive microenvironment. Defying those expectations we demonstrate that IL-10 induces several essential mechanisms for effective antitumor immune surveillance: infiltration and activation of intratumoral tumor-specific cytotoxic CD8(+) T cells, expression of the Th1 cytokine interferon-gamma (IFN gamma) and granzymes in CD8(+) T cells, and intratumoral antigen presentation molecules. Consequently, tumor immune surveillance is weakened in mice deficient for IL-10 whereas transgenic overexpression of IL-10 protects mice from carcinogenesis. Treatment with pegylated IL-10 restores tumor-specific intratumoral CD8(+) T cell function and controls tumor growth.

引用

页码：781 / 796

页数：16

共 43 条

[11] Type, density, and location of immune cells within human colorectal tumors predict clinical outcome [J].