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Innate immune sensing of cancer: clues from an identified role for type I IFNs

  • Focussed Research Review
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

A subset of patients with a variety of cancers shows evidence of a natural adaptive immune response against their tumor, as evidenced by spontaneous T-cell infiltration, circulating anti-tumor T cells, or antibody responses. Evidence has indicated that such natural immune responses have positive prognostic import in early stage disease and may be predictive of clinical response to immunotherapeutics in advanced disease. However, these observations raise a new critical fundamental question—what innate immune signals might be generated in the context of non-pathogen-induced cancers that drive productive antigen presentation toward induction of an adaptive immune response? Gene expression profiling in melanoma revealed that tumors having high expression of T-cell markers also show evidence of a type I IFN transcriptional signature. Mechanistic experiments in mice have revealed that a spontaneous CD8+ T-cell response against transplantable tumors depends on host type I IFN signaling, through a mechanism dependent upon CD8α+ dendritic cells (DCs). The requirement for type I IFN production by host DCs has suggested a subset of innate immune sensing receptors and signaling pathways that might be involved with initiating this process. Elucidating further these innate immune mechanisms should provide new insights into cancer immunotherapy.

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Acknowledgment

This work was supported by P01 CA97296 from the National Cancer Institute, USA.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, The University of Chicago, Chicago, IL, USA

    Thomas F. Gajewski, Mercedes B. Fuertes & Seng-Ryong Woo

  2. Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC2115, Chicago, IL, 60637, USA

    Thomas F. Gajewski

Authors
  1. Thomas F. Gajewski
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  2. Mercedes B. Fuertes
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  3. Seng-Ryong Woo
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Corresponding author

Correspondence to Thomas F. Gajewski.

Additional information

This paper is a Focussed Research Review based on a presentation given at the Eleventh International Conference on Progress in Vaccination against Cancer (PIVAC 11), held in Copenhagen, Denmark, 10th–13th October 2011. It is part of a CII series of Focussed Research Reviews and meeting report.

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Gajewski, T.F., Fuertes, M.B. & Woo, SR. Innate immune sensing of cancer: clues from an identified role for type I IFNs. Cancer Immunol Immunother 61, 1343–1347 (2012). https://doi.org/10.1007/s00262-012-1305-6

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  • DOI: https://doi.org/10.1007/s00262-012-1305-6

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