Opposing Roles of Type I Interferons in Cancer Immunity

• Published in: Annual review of pathology Vol. 16; no. 1; pp. 167 - 198
• Main Authors: Boukhaled, Giselle M, Harding, Shane, Brooks, David G
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 24-01-2021
• Subjects: Animals; cancer immunology; hallmarks of cancer; Humans; IFN-I; IFN-stimulated gene; immunotherapy; Interferon Type I - immunology; ISG; Neoplasms - immunology; Tumor Escape - immunology; type I interferon; type I interferon; hallmarks of cancer; cancer immunology; immunotherapy; IFN-I; ISG; IFN-stimulated gene
• ISSN: 1553-4006; 1553-4014
• DOI: 10.1146/annurev-pathol-031920-093932

The immune system is tasked with identifying malignant cells to eliminate or prevent cancer spread. This involves a complex orchestration of many immune cell types that together recognize different aspects of tumor transformation and growth. In response, tumors have developed mechanisms to circumvent immune attack. Type I interferons (IFN-Is) are a class of proinflammatory cytokines produced in response to viruses and other environmental stressors. IFN-Is are also emerging as essential drivers of antitumor immunity, potently stimulating the ability of immune cells to eliminate tumor cells. However, a more complicated role for IFN-Is has arisen, as prolonged stimulation can promote feedback inhibitory mechanisms that contribute to immune exhaustion and other deleterious effects that directly or indirectly permit cancer cells to escape immune clearance. We review the fundamental and opposing functions of IFN-Is that modulate tumor growth and impact immune function and ultimately how these functions can be harnessed for the design of new cancer therapies.