Low-dose irradiation programs macrophage differentiation to an iNOSâº/M1 phenotype that orchestrates effective T cell immunotherapy.
Cancer Cell
; 24(5): 589-602, 2013 Nov 11.
Article
in En
| MEDLINE
| ID: mdl-24209604
ABSTRACT
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⺠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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
CD4-Positive T-Lymphocytes
/
CD8-Positive T-Lymphocytes
/
Nitric Oxide Synthase Type II
/
Insulinoma
/
Macrophages
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cancer Cell
Journal subject:
NEOPLASIAS
Year:
2013
Type:
Article
Affiliation country:
Germany