Innate Immunity and Cancer: Double Edge Aspect

**383**

**Chapter 17**

**Abstract**

off-target effects.

**1. Introduction**

Metabolism

*Vaishali Chandel and Dhruv Kumar*

**Keywords:** interferons, cancer, cancer metabolism

Role of Interferon in Cancer

Interferons (IFNs), a pleotropic cytokine that has long been regarded as an important effector molecule, are increasingly recognized due to their role in cancer and in antitumor immune response regulation. Interferons broadly alter cellular functions in response to viral and other infections. Dysregulation of interferon has been implicated in cancer, autoimmune disorders, and pathogenesis of chronic viral infections. However, the association between interferons and cancer cell metabolism is poorly understood. Emerging evidence suggests the importance of lipid, energy, and amino acid metabolic pathway in regulating interferon response against cancer. Additionally, viruses exploit and modulate the host cell and induce the major metabolic reprogramming causing cancer. In response, interferons upregulate the transcription of large number of interferon stimulating gene (ISG) whose products play a major role in the innate and adaptive immune response against viral infection. Immense research is being done on understanding the role of IFNs in cancer metabolism. Therefore, systematic evaluation of these associations between interferons and cancer metabolism may have important implications for the development of anticancer therapeutics targeting IFN, minimizing toxicity, and limiting

The interferons (IFNs) are a family of pleotropic cytokines, which play an important role in anticancer immune response. IFNs broadly modulate cellular functions in response to viral and other infections. These modulations include changes in membrane composition, proliferation, metabolism, protein synthesis, and the nutritional microenvironment [1]. Interferons (IFN) are classified as three major types distinguished by their nature, sequence identity, and distribution of cognate receptors [1]. The type I human IFN encodes a family of 17 distinct proteins (IFNα 13 subtypes, IFNβ, IFNε, IFNκ, and IFNω) consisting of IFNα/β receptor 1 (IFNAR1) and IFNα/β receptor 2 (IFNAR2) subunits that bind to their cognate receptor. The type 1 IFN is located on chromosome 9p. Engagement of receptor activates the receptor-associated protein tyrosine kinases Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2), phosphorylating and activating signal transducer and activator of transcription 1 (STAT1) and STAT2 transcription factors [2]. IFNγ is the only single type II IFN, which binds to IFNγ receptor 1 (IFNGR1) and IFNγ receptor 2 IFNGR2 subunits. The type III IFNs consist of IFNλ1, IFNλ2, IFNλ3, and IFNλ4, which bind the IFNλ receptor 1 (IFNLR1) [3] (**Figure 1**). Pattern

#### **Chapter 17**
