The Efficacy of Radiotherapy Relies Upon Induction of Type I Interferon-Dependent Innate and Adaptive Immunity

By Byron Burnette, H. Liang, Youjin Lee, Lukasz K. Chlewicki, N. Khodarev, R. Weichselbaum, yang-xin fu, S. Auh. Cancer Research, 2011

778 citations recorded by the source corpus.

Summary 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 demonstrated 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 interferon (IFN) in local tumor control mediated by local RT. We show that ablative RT increases intratumoral production of IFNβ and, more surprisingly, the anti-tumor effect of RT is abolished in type I IFN non-responsive 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 DC from wild-type mice but not type I IFN receptor deficient mice. The enhanced cross-priming ability of tumor infiltrating DCs after RT was dependent on autocrine production of type I IFNs. Using adenoviral-mediated expression of IFNβ, we demonstrate that delivery of exogenous IFNβ 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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/935aac4b862df97d858c9e44d4dc7f96fc747a5a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Zhijian J. Chen
2. Xiao-Dong Li
3. yang-xin fu
4. H. Liang
5. R. Weichselbaum
6. T. Gajewski
7. Byron Burnette
8. T. Darga

In Oncology

1. Zhijian J. Chen
2. yang-xin fu
3. H. Liang
4. R. Weichselbaum
5. T. Gajewski
6. Byron Burnette
7. T. Darga
8. M. Beckett

Citations in the corpus

• Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. (2014, neutral): “radiation-induced antitumor immunity (2).”
• STING-dependent Cytosolic DNA Sensing Promotes Radiation-induced Type I interferon-dependent Antitumor Immunity in Immunogenic Tumors (2014, background): “The induction of type I IFNs by radiation is essential for the function of CD8 T cells (Burnette et al., 2011).”
• Cytokines in Radiobiological Responses: A Review (2012, neutral): “They bind IFNs, IL10 homologs and IL-28-29 family members.”