Type I interferon-mediated tumor immunity and its role in immunotherapy

Cell Mol Life Sci. 2022 Mar 16;79(3):191. doi: 10.1007/s00018-022-04219-z.


Immune checkpoint blockade (ICB) therapies have achieved remarkable clinical responses in patients with many different types of cancer; however, most patients who receive ICB monotherapy fail to achieve long-term responses, and some tumors become immunotherapy-resistant and even hyperprogressive. Type I interferons (IFNs) have been demonstrated to inhibit tumor growth directly and indirectly by acting upon tumor and immune cells, respectively. Furthermore, accumulating evidence indicates that endo- and exogenously enhancing type I IFNs have a synergistic effect on anti-tumor immunity. Therefore, clinical trials studying new treatment strategies that combine type I IFN inducers with ICB are currently in progress. Here, we review the cellular sources of type I IFNs and their roles in the immune regulation of the tumor microenvironment. In addition, we highlight immunotherapies based on type I IFNs and combination therapy between type I IFN inducers and ICBs.

Keywords: IFN-α; IFN-β; Oncolytic virotherapy; Radiation therapy; STING; Tumor immunity; cGAS.

Publication types

  • Review

MeSH terms

  • Animals
  • Cancer-Associated Fibroblasts / immunology
  • Combined Modality Therapy
  • Dendritic Cells / immunology
  • Endothelial Cells / immunology
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy / methods*
  • Interferon Type I / biosynthesis
  • Interferon Type I / immunology*
  • Killer Cells, Natural / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Macrophages / immunology
  • Mice
  • Models, Immunological
  • Myeloid-Derived Suppressor Cells / immunology
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Neutrophils / immunology
  • Oncolytic Virotherapy
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Toll-Like Receptors / agonists
  • Tumor Microenvironment / immunology


  • Immune Checkpoint Inhibitors
  • Interferon Type I
  • Toll-Like Receptors