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

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

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.

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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

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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.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, University of Rochester, Rochester, 601 Elmwood Ave, Box 672, Rochester, NY, 14642, USA

    Joanne Y. H. Lim, Scott A. Gerber, Shawn P. Murphy & Edith M. Lord

  2. Department of Obstetrics and Gynecology, University of Rochester, Rochester, NY, USA

    Shawn P. Murphy

Authors
  1. Joanne Y. H. Lim
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  2. Scott A. Gerber
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  3. Shawn P. Murphy
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  4. Edith M. Lord
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Corresponding author

Correspondence to Edith M. Lord.

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Lim, J.Y.H., Gerber, S.A., Murphy, S.P. et al. Type I interferons induced by radiation therapy mediate recruitment and effector function of CD8+ T cells. Cancer Immunol Immunother 63, 259–271 (2014). https://doi.org/10.1007/s00262-013-1506-7

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  • DOI: https://doi.org/10.1007/s00262-013-1506-7

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