Low-Dose Irradiation Programs Macrophage Differentiation to an iNOS+/M1 Phenotype that Orchestrates Effective T Cell Immunotherapy
Low-Dose Irradiation Programs Macrophage Differentiation to an iNOS+/M1 Phenotype that Orchestrates Effective T Cell Immunotherapy
复制标题
DOI：
10.1016/j.ccr.2013.09.014
复制
发表时间：
2013-11-11
期刊：
影响因子：
50.3
通讯作者：
Beckhove, Philipp
中科院分区：
文献类型：
--
作者：
Klug, Felix;Prakash, Hridayesh;Beckhove, Philipp
低效的T细胞迁移是癌症免疫治疗的主要限制。靶向激活肿瘤微环境可以克服这一障碍。我们证明，新辅助局部低剂量γ射线照射（LDI）导致正常化的异常血管和肿瘤特异性T细胞在人胰腺癌和T细胞介导的肿瘤排斥反应和延长生存期，否则免疫难治性自发和异种移植小鼠肿瘤模型的有效招聘。LDI（局部或过继前转移）通过诱导内皮活化和TH1趋化因子的表达以及通过抑制血管生成、免疫抑制和肿瘤生长因子的产生，对iNOS（+）M1巨噬细胞的分化进行编程，所述巨噬细胞通过iNOS协调CTL募集到实体瘤中并在实体瘤中杀伤。
Inefficient T cell migration is a major limitation of cancer immunotherapy. Targeted activation of the tumor microenvironment may overcome this barrier. We demonstrate that neoadjuvant local low-dose gamma irradiation (LDI) causes normalization of aberrant vasculature and efficient recruitment of tumor-specific T cells in human pancreatic carcinomas and T-cell-mediated tumor rejection and prolonged survival in otherwise immune refractory spontaneous and xenotransplant mouse tumor models. LDI (local or pre-adoptive-transfer) programs the differentiation of iNOS(+) M1 macrophages that orchestrate CTL recruitment into and killing within solid tumors through iNOS by inducing endothelial activation and the expression of TH1 chemokines and by suppressing the production of angiogenic, imnnunosuppressive, and tumor growth factors.