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

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.

Automated summary

Type I interferons inhibit tumor growth directly and indirectly by acting upon tumor and immune cells, with evidence showing that enhancing both endo- and exogenously produced type I IFNs have a synergistic effect on anti-tumor immunity. Clinical trials are currently exploring new treatment strategies combining type I IFN inducers with ICBs, highlighting the importance of understanding the cellular sources and roles of type I IFNs in the immune regulation of the tumor microenvironment.