The efficacy of radiotherapy relies upon induction of type I interferon-dependent innate and adaptive immunity

Byron C. Burnette, Hua Liang, Youjin Lee, Lukasz Chlewicki, Nikolai N. Khodarev, Ralph R. Weichselbaum, Yang Xin Fu, Sogyong L. Auh

Research output: Contribution to journalArticle

327 Citations (Scopus)

Abstract

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-β 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-β, we show that delivery of exogenous IFN-β 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.

Original languageEnglish (US)
Pages (from-to)2488-2496
Number of pages9
JournalCancer Research
Volume71
Issue number7
DOIs
StatePublished - Apr 1 2011

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Interferon Type I
Adaptive Immunity
Innate Immunity
Radiotherapy
Neoplasms
Cross-Priming
T-Lymphocytes
Dendritic Cells
DNA Damage
Radiation
Antigens

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Burnette, B. C., Liang, H., Lee, Y., Chlewicki, L., Khodarev, N. N., Weichselbaum, R. R., ... Auh, S. L. (2011). The efficacy of radiotherapy relies upon induction of type I interferon-dependent innate and adaptive immunity. Cancer Research, 71(7), 2488-2496. https://doi.org/10.1158/0008-5472.CAN-10-2820

The efficacy of radiotherapy relies upon induction of type I interferon-dependent innate and adaptive immunity. / Burnette, Byron C.; Liang, Hua; Lee, Youjin; Chlewicki, Lukasz; Khodarev, Nikolai N.; Weichselbaum, Ralph R.; Fu, Yang Xin; Auh, Sogyong L.

In: Cancer Research, Vol. 71, No. 7, 01.04.2011, p. 2488-2496.

Research output: Contribution to journalArticle

Burnette, BC, Liang, H, Lee, Y, Chlewicki, L, Khodarev, NN, Weichselbaum, RR, Fu, YX & Auh, SL 2011, 'The efficacy of radiotherapy relies upon induction of type I interferon-dependent innate and adaptive immunity', Cancer Research, vol. 71, no. 7, pp. 2488-2496. https://doi.org/10.1158/0008-5472.CAN-10-2820
Burnette, Byron C. ; Liang, Hua ; Lee, Youjin ; Chlewicki, Lukasz ; Khodarev, Nikolai N. ; Weichselbaum, Ralph R. ; Fu, Yang Xin ; Auh, Sogyong L. / The efficacy of radiotherapy relies upon induction of type I interferon-dependent innate and adaptive immunity. In: Cancer Research. 2011 ; Vol. 71, No. 7. pp. 2488-2496.
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