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Review
. 2019 Jun:43:101299.
doi: 10.1016/j.smim.2019.101299.

Interferon signaling in cancer. Non-canonical pathways and control of intracellular immune checkpoints

Diana Saleiro  1 , Leonidas C Platanias  2
Affiliations
Review

Interferon signaling in cancer. Non-canonical pathways and control of intracellular immune checkpoints

Diana Saleiro et al. Semin Immunol. 2019 Jun.

Abstract

The interferons (IFNs) are cytokines with important antineoplastic and immune modulatory effects. These cytokines have been conserved through evolution as important elements of the immune surveillance against cancer. Despite this, defining their precise and specific roles in the generation of antitumor responses remains challenging. Emerging evidence suggests the existence of previously unknown roles for IFNs in the control of the immune response against cancer that may redefine our understanding on how these cytokines function. Beyond the engagement of classical JAK-STAT signaling pathways that promote transcription and expression of gene products, the IFNs engage multiple other signaling cascades to generate products that mediate biological responses and outcomes. There is recent emerging evidence indicating that IFNs control the expression of both traditional immune checkpoints like the PD-L1/PD1 axis, but also less well understood "intracellular" immune checkpoints whose targeting may define new approaches for the treatment of malignancies.

Keywords: Cancer; Immune checkpoint; Immune response; Interferon; Non-canonical pathways; Signaling.

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Conflict of interest statement

Conflict of interest statement

Declarations of interest: none.

Figures

Figure 1:
Figure 1:
Non-canonical pathways and related interactions in the generation of Type I IFN antineoplastic responses. ISG - Interferon stimulated genes, STAT - signal transducers and activators of transcription, MAPK - Mitogen activated protein kinase, SLFN - Schlafen, mTOR - mammalian target of rapamycin, GCD - GTPases/Cyclin Dependent Kinases.
Figure 2:
Figure 2:
ULK1 pathways in Type I and II IFN signaling. UULKK – Upstream ULK1 kinase; ISGs – IFN-stimulated genes; IRE - IFN responsive elements; PE – Positive Effectors; NFE - Negative Feedback effectors
Figure 3:
Figure 3:
Proposed model on the roles of classical immune checkpoints and putative “intracellular immune checkpoints” related to IFN-signaling pathways. IICs - Intracellular Immune Checkpoints, NC-ISPs - Non-Canonical IFN Signaling Pathways
See this image and copyright information in PMC

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