Tumoral expression of IL-33 inhibits tumor growth and modifies the tumor microenvironment through CD8+ T and NK cells.
Tumoral expression of IL-33 inhibits tumor growth and modifies the tumor microenvironment through CD8+ T and NK cells.
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IL-33 的肿瘤表达通过 CD8 T 和 NK 细胞抑制肿瘤生长并改变肿瘤微环境
DOI：
10.4049/jimmunol.1401344
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Lu B
中科院分区：
文献类型：
--
作者：
Gao X;Wang X;Yang Q;Zhao X;Wen W;Li G;Lu J;Qin W;Qi Y;Xie F;Jiang J;Wu C;Zhang X;Chen X;Turnquist H;Zhu Y;Lu B
癌症免疫治疗作为一种新的标准癌症治疗方式已显示出巨大的前景。然而，目前依赖于增强自发抗肿瘤免疫应答的方法的应答率有限。因此，通过表达适当的细胞因子来增加肿瘤免疫原性将进一步改善当前的免疫治疗。IL-33是细胞因子IL-1家族的成员，由坏死的上皮细胞或激活的先天免疫细胞释放，因此被认为是“危险”信号。IL-33在促进2型免疫应答和组织炎症中的作用已得到充分证实。然而，IL-33是否驱动抗肿瘤免疫应答是有争议的。我们之前的工作确定IL-33促进CD 8 + T细胞的功能。在这项研究中，我们发现IL-33在两种类型的癌细胞中的表达有效地抑制了肿瘤的生长和转移。在机制上，IL-33增加了肿瘤组织中CD 8 + T和NK细胞的数量和IFN-γ的产生，从而诱导有利于肿瘤根除的肿瘤微环境。重要的是，IL-33大大增加了肿瘤Ag特异性CD 8 + T细胞。此外，NK和CD 8 + T细胞都是IL-33的抗肿瘤作用所必需的。此外，调节性T细胞的耗竭与IL-33表达协同作用以消除肿瘤。我们的研究通过促进根除癌症的1型免疫应答将“alarmin”IL-33确立为用于肿瘤免疫治疗的有前途的新细胞因子。
Cancer immunotherapy has shown great promise as a new standard cancer therapeutic modality. However, the response rates are limited for current approach that depends on enhancing spontaneous antitumor immune responses. Therefore, increasing tumor immunogenicity by expressing appropriate cytokines should further improve the current immunotherapy. IL-33 is a member of the IL-1 family of cytokines and is released by necrotic epithelial cells or activated innate immune cells and is thus considered a “danger” signal. The role of IL-33 in promoting type 2 immune responses and tissue inflammation has been well established. However, whether IL-33 drives antitumor immune responses is controversial. Our previous work established that IL-33 promoted the function of CD8+ T cells. In this study, we showed that the expression of IL-33 in two types of cancer cells potently inhibited tumor growth and metastasis. Mechanistically, IL-33 increased numbers and IFN-γ production by CD8+ T and NK cells in tumor tissues, thereby inducing a tumor microenvironment favoring tumor eradication. Importantly, IL-33 greatly increased tumor Ag-specific CD8+ T cells. Furthermore, both NK and CD8+ T cells were required for the antitumor effect of IL-33. Moreover, depletion of regulatory T cells worked synergistically with IL-33 expression for tumor elimination. Our studies established “alarmin” IL-33 as a promising new cytokine for tumor immunotherapy through promoting cancer-eradicating type 1 immune responses.
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TIM-3 表达是肿瘤组织中调节性 T 细胞的特征，并与肺癌进展相关
影响因子：
3.7
作者：
Gao X;Zhu Y;Li G;Huang H;Zhang G;Wang F;Sun J;Yang Q;Zhang X;Lu B
通讯作者：
Lu B
影响因子：
50.3
作者：
Granot Z;Henke E;Comen EA;King TA;Norton L;Benezra R
通讯作者：
Benezra R
影响因子：
9.7
作者：
Gao, Kun;Li, Xiaoying;Zhang, Lianfeng
通讯作者：
Zhang, Lianfeng
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM
影响因子：
--
作者：
Tanchot, C.;Terme, M.;Tartour, E.
通讯作者：
Tartour, E.