PMID- 21300764
OWN - NLM
STAT- MEDLINE
DCOM- 20110711
LR  - 20231120
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 71
IP  - 7
DP  - 2011 Apr 1
TI  - The efficacy of radiotherapy relies upon induction of type i interferon-dependent 
      innate and adaptive immunity.
PG  - 2488-96
LID - 10.1158/0008-5472.CAN-10-2820 [doi]
AB  - The most widely held explanation for the efficacy of local radiotherapy (RT) is 
      based on direct cytotoxicity to cancer cells through the induction of lethal DNA 
      damage. Recent studies have shown that local ablative radiation of established 
      tumors can lead to increased T-cell priming and T-cell-dependent tumor 
      regression, but the underlying mechanism remains unclear. Here, we describe an 
      essential role for type I IFN in local RT-mediated tumor control. We show that 
      ablative RT increases intratumoral production of IFN-beta and, more surprisingly, 
      the antitumor effect of RT is abolished in type I IFN nonresponsive hosts. 
      Furthermore, the major target of RT-induced type I IFN is the hematopoietic 
      compartment. RT drastically enhances the cross-priming capacity of 
      tumor-infiltrating dendritic cells (TIDC) from wild-type mice but not type I IFN 
      receptor-deficient mice. The enhanced cross-priming ability of TIDCs after RT was 
      dependent on autocrine production of type I IFNs. By using adenoviral-mediated 
      expression of IFN-beta, we show that delivery of exogenous IFN-beta into the tumor 
      tissue in the absence of RT is also sufficient to selectively expand 
      antigen-specific T cells leading to complete tumor regression. Our study reveals 
      that local high-dose RT can trigger production of type I IFN that initiates a 
      cascading innate and adaptive immune attack on the tumor.
FAU - Burnette, Byron C
AU  - Burnette BC
AD  - Departments of Pathology and Radiation and Cellular Oncology, The Ludwig Center 
      for Metastasis Research, University of Chicago, Chicago, Illinois, USA.
FAU - Liang, Hua
AU  - Liang H
FAU - Lee, Youjin
AU  - Lee Y
FAU - Chlewicki, Lukasz
AU  - Chlewicki L
FAU - Khodarev, Nikolai N
AU  - Khodarev NN
FAU - Weichselbaum, Ralph R
AU  - Weichselbaum RR
FAU - Fu, Yang-Xin
AU  - Fu YX
FAU - Auh, Sogyong L
AU  - Auh SL
LA  - eng
GR  - CA134563/CA/NCI NIH HHS/United States
GR  - R01 CA134563-03/CA/NCI NIH HHS/United States
GR  - R01 CA134563-02/CA/NCI NIH HHS/United States
GR  - 5 T32 GM07281/GM/NIGMS NIH HHS/United States
GR  - CA115540/CA/NCI NIH HHS/United States
GR  - R01 CA111423/CA/NCI NIH HHS/United States
GR  - R01 CA141975/CA/NCI NIH HHS/United States
GR  - R01 CA115540/CA/NCI NIH HHS/United States
GR  - R01 CA134563/CA/NCI NIH HHS/United States
GR  - R01 CA134563-01A2/CA/NCI NIH HHS/United States
GR  - P01 CA097296/CA/NCI NIH HHS/United States
GR  - R01 CA115540-05/CA/NCI NIH HHS/United States
GR  - T32 GM007281/GM/NIGMS NIH HHS/United States
GR  - CA111423/CA/NCI NIH HHS/United States
GR  - CA97296/CA/NCI NIH HHS/United States
GR  - R01 CA141975-02/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110207
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Interferon Type I)
RN  - 0 (Interferon-alpha)
RN  - 77238-31-4 (Interferon-beta)
SB  - IM
MH  - Adaptive Immunity/radiation effects
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/immunology/radiation effects
MH  - Dendritic Cells/immunology/radiation effects
MH  - Epitopes, T-Lymphocyte/immunology
MH  - Hematopoietic Stem Cells/immunology/radiation effects
MH  - Immunity, Innate/radiation effects
MH  - Interferon Type I/biosynthesis/*immunology/pharmacology
MH  - Interferon-alpha/biosynthesis/immunology
MH  - Interferon-beta/biosynthesis/immunology/pharmacology
MH  - Melanoma, Experimental/*immunology/*radiotherapy
MH  - Mice
MH  - Mice, Knockout
MH  - Tumor Microenvironment/immunology/radiation effects
PMC - PMC3070872
MID - NIHMS271137
COIS- Disclosure of Potential conflicts of Interest The authors declare that they have 
      no competing financial interests.
EDAT- 2011/02/09 06:00
MHDA- 2011/07/12 06:00
PMCR- 2012/04/01
CRDT- 2011/02/09 06:00
PHST- 2011/02/09 06:00 [entrez]
PHST- 2011/02/09 06:00 [pubmed]
PHST- 2011/07/12 06:00 [medline]
PHST- 2012/04/01 00:00 [pmc-release]
AID - 0008-5472.CAN-10-2820 [pii]
AID - 10.1158/0008-5472.CAN-10-2820 [doi]
PST - ppublish
SO  - Cancer Res. 2011 Apr 1;71(7):2488-96. doi: 10.1158/0008-5472.CAN-10-2820. Epub 
      2011 Feb 7.