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首页> 外文期刊>Cancer Cell >Low-Dose Irradiation Programs Macrophage Differentiation to an iNOS+/M1 Phenotype that Orchestrates Effective T Cell Immunotherapy
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Low-Dose Irradiation Programs Macrophage Differentiation to an iNOS+/M1 Phenotype that Orchestrates Effective T Cell Immunotherapy

机译：低剂量照射可将巨噬细胞分化为可协调有效T细胞免疫疗法的iNOS + / M1表型

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摘要

Inefficient Tcell 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 Tcells 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, immunosuppressive, and tumor growth factors.
机译：T细胞迁移效率低下是癌症免疫治疗的主要局限。肿瘤微环境的靶向激活可以克服这一障碍。我们证明，新辅助局部低剂量伽马射线照射（LDI）会导致异常的脉管系统正常化，并在人胰腺癌中有效募集肿瘤特异性T细胞和T细胞介导的肿瘤排斥反应，并在其他免疫性难治性自发和异种移植小鼠肿瘤中延长生存时间楷模。 LDI（局部或前转移）通过诱导内皮细胞活化和TH1趋化因子的表达，并抑制血管生成，免疫抑制和生成，从而通过iNOS来分化iNOS + M1巨噬细胞，从而将CTL募集并杀入实体瘤中。肿瘤生长因子。

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