Interferon Lambda: Toward a Dual Role in Cancer

Interferon (IFN)-lambda, a type III interferon (IFN), is a member of a new family of pleotropic cytokines that share high similarity with classical IFNs alpha and beta (IFN-alpha/beta), type I IFNs. IFN-lambda acts as an antiviral agent and displays distinct biological functions, including tumor suppression. Although it activates the common Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways, similar to IFN-alpha/beta, IFN-lambda differentially induces the expression of IFN-stimulated genes (ISGs). Novel evidence indicates that IFN-lambda acts quite differently from IFN-alpha/beta under both homeostasis and pathological situations. In contrast to IFN-alpha/beta, IFN-lambda is not involved in over-stimulation of the immune response or exacerbation of inflammation. However, the emergence of unexpected characteristics of IFN-lambda, in the control of inflammation and promotion of immune suppression and cancer, reveals novel challenges and offers more strategic opportunities in the context of cancer and beyond. In this article, we discuss new evidence and potential consequences associated with the biology of IFN-lambda and provide a different vision for building novel therapeutic strategies in oncology.