Innate immune sensing of cancer: clues from an identified role for type I IFNs

A subset of patients with a variety of cancers shows evidence of a natural adaptive immune response against their tumor, as evidenced by spontaneous T-cell infiltration, circulating anti-tumor T cells, or antibody responses. Evidence has indicated that such natural immune responses have positive prognostic import in early stage disease and may be predictive of clinical response to immunotherapeutics in advanced disease. However, these observations raise a new critical fundamental question—what innate immune signals might be generated in the context of non-pathogen-induced cancers that drive productive antigen presentation toward induction of an adaptive immune response? Gene expression profiling in melanoma revealed that tumors having high expression of T-cell markers also show evidence of a type I IFN transcriptional signature. Mechanistic experiments in mice have revealed that a spontaneous CD8⁺ T-cell response against transplantable tumors depends on host type I IFN signaling, through a mechanism dependent upon CD8α⁺ dendritic cells (DCs). The requirement for type I IFN production by host DCs has suggested a subset of innate immune sensing receptors and signaling pathways that might be involved with initiating this process. Elucidating further these innate immune mechanisms should provide new insights into cancer immunotherapy.