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Cancer Immunology, Immunotherapy

, Volume 63, Issue 3, pp 259–271 | Cite as

Type I interferons induced by radiation therapy mediate recruitment and effector function of CD8+ T cells

  • Joanne Y. H. Lim
  • Scott A. Gerber
  • Shawn P. Murphy
  • Edith M. LordEmail author
Original Article

Abstract

The need for an intact immune system for cancer radiation therapy to be effective suggests that radiation not only acts directly on the tumor but also indirectly, through the activation of host immune components. Recent studies demonstrated that endogenous type I interferons (type I IFNs) play a role in radiation-mediated anti-tumor immunity by enhancing the ability of dendritic cells to cross-prime CD8+ T cells. However, it is still unclear to what extent endogenous type I IFNs contribute to the recruitment and function of CD8+ T cells. Little is also known about the effects of type I IFNs on myeloid cells. In the current study, we demonstrate that type I and type II IFNs (IFN-γ) are both required for the increased production of CXCL10 (IP-10) chemokine by myeloid cells within the tumor after radiation treatment. Radiation-induced intratumoral IP-10 levels in turn correlate with tumor-infiltrating CD8+ T cell numbers. Moreover, type I IFNs promote potent tumor-reactive CD8+ T cells by directly affecting the phenotype, effector molecule production, and enhancing cytolytic activity. Using a unique inducible expression system to increase local levels of IFN-α exogenously, we show here that the capacity of radiation therapy to result in tumor control can be enhanced. Our preclinical approach to study the effects of local increase in IFN-α levels can be used to further optimize the combination therapy strategy in terms of dosing and scheduling, which may lead to better clinical outcome.

Keywords

Radiation therapy Interferon B16 melanoma CXCR3 CD8+ T cells 

Abbreviations

IFN

Interferon

MFI

Mean fluorescence intensity

RT

Radiation therapy

SBRT

Stereotactic body radiation therapy

tdLN

Tumor-draining lymph nodes

TILs

Tumor-infiltrating lymphocytes

Veh

Vehicle control

Notes

Acknowledgments

The authors thank Dr. John G. Frelinger for suggestions and thoughtful discussions pertinent to this study. This project was financially supported by National Institutes of Health, Grant CA 28332.

Conflict of interest

The authors disclose no conflicts of interest.

Supplementary material

262_2013_1506_MOESM1_ESM.pdf (335 kb)
Supplementary material 1 (PDF 335 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Joanne Y. H. Lim
    • 1
  • Scott A. Gerber
    • 1
  • Shawn P. Murphy
    • 1
    • 2
  • Edith M. Lord
    • 1
    Email author
  1. 1.Department of Microbiology and ImmunologyUniversity of RochesterRochesterUSA
  2. 2.Department of Obstetrics and GynecologyUniversity of RochesterRochesterUSA

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