10-28-2013, 06:37 PM
Low-Dose Irradiation Programs Macrophage Differentiation to an iNOS+/M1 Phenotype that Orchestrates Effective T Cell Immunotherapy
<b>Cancer Cell, </b>24 October 2013
Copyright 2013 Elsevier Inc. All rights reserved.
10.1016/j.ccr.2013.09.014
<ul class="bbc">
[*]Highlights
[*]Local LDI efficiently recruits effector Tcells into tumors
[*]LDI enables efficient T-cell-mediated tumor rejection and improved survival
[*]LDI acts through iNOS induction in tumor-associated macrophages
[*]INOS raises TH1 chemokines and inhibits angiogenic and immune suppressive cytokines
</ul> SummaryInefficient 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.
Cell dot com
<b>Cancer Cell, </b>24 October 2013
Copyright 2013 Elsevier Inc. All rights reserved.
10.1016/j.ccr.2013.09.014
<ul class="bbc">
[*]Highlights
[*]Local LDI efficiently recruits effector Tcells into tumors
[*]LDI enables efficient T-cell-mediated tumor rejection and improved survival
[*]LDI acts through iNOS induction in tumor-associated macrophages
[*]INOS raises TH1 chemokines and inhibits angiogenic and immune suppressive cytokines
</ul> SummaryInefficient 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.
Cell dot com