Type I interferons induced by radiation therapy mediate recruitment and effector function of CD8(+) T cells.
Type I interferons induced by radiation therapy mediate recruitment and effector function of CD8(+) T cells.
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DOI：
10.1007/s00262-013-1506-7
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发表时间：
2014-03
影响因子：
5.8
通讯作者：
Lord, Edith M.
中科院分区：
文献类型：
--
作者：
Lim, Joanne Y. H.;Gerber, Scott A.;Murphy, Shawn P.;Lord, Edith M.
癌症放射治疗需要一个完整的免疫系统才能有效，这表明放射不仅直接作用于肿瘤，而且通过激活宿主免疫成分间接作用于肿瘤。最近的研究表明，内源性I型干扰素（I型IFN）通过增强树突状细胞（DC）交叉致敏CD 8 + T细胞的能力在辐射介导的抗肿瘤免疫中发挥作用。然而，目前还不清楚内源性I型IFN在多大程度上有助于CD 8 + T细胞的募集和功能。关于I型干扰素对骨髓细胞的影响也知之甚少。在目前的研究中，我们证明了I型和II型IFN（IFN-γ）都是放射治疗后肿瘤内髓样细胞产生CXCL 10（IP-10）趋化因子增加所必需的。放射诱导的肿瘤内IP-10水平反过来与肿瘤浸润的CD 8 + T细胞数量相关。此外，I型IFN通过直接影响表型、效应分子产生和增强细胞溶解活性来促进有效的肿瘤反应性CD 8 + T细胞。使用一种独特的诱导表达系统，以增加局部水平的IFN-α外源性，我们在这里表明，放射治疗的能力，导致肿瘤控制可以提高。我们研究局部IFN-α水平升高的临床前方法可用于进一步优化联合治疗策略的剂量和时间安排，这可能会导致更好的临床结局。
The need for an intact immune system for cancer radiation therapy to be effective suggests that radiation not only acts directly on the tumor but also indirectly, through activation of host immune components. Recent studies demonstrated that endogenous type I interferons (type I IFNs) play a role in radiation-mediated anti-tumor immunity by enhancing the ability of dendritic cells (DCs) to cross-prime CD8+ T cells. However, it is still unclear to what extent endogenous type I IFNs contribute to the recruitment and function of CD8+ T cells. Little is also known about the effects of type I IFNs on myeloid cells. In the current study, we demonstrate that type I and type II IFN (IFN-γ) are both required for the increased production of CXCL10 (IP-10) chemokine by myeloid cells within the tumor after radiation treatment. Radiation-induced intratumoral IP-10 levels in turn correlate with tumor-infiltrating CD8+ T cell numbers. Moreover, type I IFNs promote potent tumor-reactive CD8+ T cells by directly affecting the phenotype, effector molecule production and enhancing cytolytic activity. Using a unique inducible expression system to increase local levels of IFN-α exogenously, we show here that the capacity of radiation therapy to result in tumor control can be enhanced. Our pre-clinical approach to study the effects of local increase in IFN-α levels can be used to further optimize the combination therapy strategy in terms of dosing and scheduling, which may lead to better clinical outcome.
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DOI：
10.1084/jem.20101159
发表时间：
2011-09-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fuertes MB;Kacha AK;Kline J;Woo SR;Kranz DM;Murphy KM;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
11.2
作者：
Burnette BC;Liang H;Lee Y;Chlewicki L;Khodarev NN;Weichselbaum RR;Fu YX;Auh SL
通讯作者：
Auh SL
影响因子：
7
作者：
Curtsinger JM;Mescher MF
通讯作者：
Mescher MF
影响因子：
56.9
作者：
MULLER, U;STEINHOFF, U;AGUET, M
通讯作者：
AGUET, M
DOI：
10.4049/jimmunol.1100845
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kline J;Zhang L;Battaglia L;Cohen KS;Gajewski TF
通讯作者：
Gajewski TF